Accesion 112110

Conan4-5 mo MI Australian Shepherd presents for recent onset of

murmurHx: Chronic recurrent fevers, musculoskeletal pain, lethargy, has

been on Prednisone 1 mg/kg BID chronically, recently up to 2 mg/kg BID, several doses of Clavamox. Intermittent episodes of dyspnea and cyanosis, and subcutaneous abcessation

PE: small stature, small testes, carpal hyperextension, shoulder and stifle effusion, pain on flexion and extension of multiple joints

Echo: Moderate MR with HCM; dynamic LVOT obstruction d/t MV displacement, either dysplastic valve or secondary to HCM

Chemistry: low Creat, high Phos*, low norm Alb, mild high ALP*, Low Amy* (*could be artifactual d/t hemolysis)

CBC: PLT=943, PCV=37, PMN=1.643, Lymph-0.091, Mono=7.121

Arthrocentesis: Mild chronic inflammation (large mononuclear)

Radiographs

Juvenile hyperadrenocorticism-veterinary sources1,2

Hyperadrenocorticism is a differential for a pediatric growth failure resulting in small stature and good body conditionPartly through inhibition of GH releaseRetarded growth and delayed growth plate

closure may occur in young dogsOsteopenia is attributable to decreased bone

formation, bone resorption is apparently normal

Spontaneous fractures, increased prevalence of IVDD has also been reported

Signs and symptoms of pediatric Cushing’s Syndrome-CS3

Weight gain and growth failure: reduction in height SDS with increased BMI SDS

HypertensionOsteoporosisAbnormal pubertal developmentHirsuitism and virilization (excessive hair

growth for level of gonadal and breast development)

Hypertension

Pediatric Cushing’s Syndrome and bone diseaseGuyton: osteoporosis with Cushing’s

syndrome d/t :decreased deposition of protein throughout the

body; increased catabolism of proteinDepression on osteoblastic activity

Cushing’s syndrome in children can result in severe loss in bone mineral density7

Bone loss more severe in primary adrenal Cushing’s syndrome than PDH

Skeletal maturation at diagnosis of pediatric Cushing’s diseaseChildren with Cushing’s syndrome present with obesity

and decreased linear growth, renal stones (increased calciuria), gonadal dysfunction (especially males)

75-80% of pediatric Cushing’s syndrome is caused by ACTH-secreting pituitary corticotroph adenoma

Delay in skeletal growth due to decreases in GH and d/t direct effects on the growth plate by glucocorticoids

Down-regulation of hypothalamic-pituitary-gonadal axis: delay in puberty

Bone age delay =difference between chronological age and bone age;

present in most cases reviewed correlated negatively with height and positively with

duration of syndrome

PathophysiologyBone age delay

may not be present in puberty, but is commonly delayed in prepubertal population

ACTH stimulation may cause upregulation of adrenal androgen secretion, may accelerate linear growth and skeletal maturation

In vivo, patients may have GH deficiency, IGF_1 levels may be normal, both have been shown to be suppressed by glucocorticoids in

rats, effects may also be due to downregulation of GH binding proteins

Downregulation of vascular endothelial growth factor production

Lead to disruption of normal invasion of blood vessels in the growth plate with disturbance of endochondral ossification and growth

Reduction of number and function of mature osteoblast cellsStimulation and prolongation osteoclast formation, activity and

survival

Pediatric Cushing’s syndrome-Outcome

Subnormal growth rate and short stature reported even after transsphenoidal surgery and radiation therapy

Measurements for GH deficiency and replacement if present has resulted in acceptable growth

Many patients remain obese, with elevated BMI post cure

BMD, bone mineral density, is often, but not always, reduced in children after cure; possible risk for longterm osteoporosis

References1. Ihle SL. Failure to Grow. In Textbook of Veterinary Internal Medicine.

Ettinger and Feldman. Elselvier Saunders, St. Louis, 2005. pp 80-83. 2. Johnson KA, Watson ADJ. Skeletal Diseases. In Textbook of

Veterinary Internal Medicine. Ettinger and Feldman. Elselvier Saunders, St. Louis, 2005. pp 80-83.

3. Chan LF, et al. Pediatric Cushing’s Syndrome: Clinical Features, Diagnosis, and Treatment. Arq Bras Endocrinol Metab 2007;51/8:1261-1271

4. Guyton AC, Hall JE. Parathyroid Hormone, Calcitonin, Calcium and Phosphate Metabolism, Vitamin D, Bone, and Teeth. In Textbook of Medical Physiology. W. B. Saunders. Philadelphia, 2000. pp 899-915.

5. Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing’s Syndrome. Lancet 2006; 367: 1605–17.

6. Peters CJ, et al. Factors Influencing Skeletal Matruation at Diagnosis of Paediatric Cushing’s Disease. Horm Res 2007;68:231–235.

7. Leong GM, et al. The effect of Cushing’s Disease on Bone Mineral Density, Body Composition, Growth and Puberty: A Report of an Identical Adolescent Twin Pair. J Clin Endocrinol Metab 1996; 81: 1905-1911.