JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

September 2022

I-M21 (NP)

 

Signalment (JPC # 1620815-00):  3-year-old German Shepherd cross dog.

 

HISTORY: This dog weighed 4.4lb. at 3 years of age and still had deciduous teeth and epiphyseal lines on radiography in addition to alopecia over the ears, back, abdomen and legs.

 

HISTOPATHOLOGIC DESCRIPTION:  Haired skin: Diffusely, hair follicles are restricted to the superficial dermis, have prominent tricholemmal keratin (telogen phase), and are small, thin walled, poorly formed, and lack internal root sheaths (follicular atrophy). Most hair follicles also lack hair shafts (hypotrichosis), are ectatic, lined by attenuated epithelium, and contain abundant lamellated keratin (follicular keratosis). The epidermis is thin with moderate orthokeratotic hyperkeratosis and melanin pigment present within all layers of the epidermis (hyperpigmentation). Dermal collagen fibers are loose and haphazardly arranged. 

 

MORPHOLOGIC DIAGNOSIS:  Haired skin:  Atrophy, follicular, diffuse, moderate, with hypotrichosis, telogenization, and orthokeratotic hyperkeratosis, German shepherd dog, canine.

 

CONDITION:  Juvenile panhypopituitarism

 

SYNONYMS:  Pituitary dwarfism, hyposomatotropism

 

GENERAL DISCUSSION: 

• Most common in German shepherd dogs; also reported in Tibetan terriers, Karelian bear dogs, Spitz, toy pinscher, Saarloos, Czechoslovakian wolfdogs, and toy poodles 
• Dogs have a shorter life span due to due panhypopituitarism and secondary endocrine dysfunction, such as hypothyroidism and hypoadrenocortism

 

PATHOGENESIS:

• Pituitary dwarfism (congenital hypopituitarism – E-M02) is an inherited simple autosomal recessive endocrine disease due to a 7 base pair deletion on intron 5 of the LHX3 gene 
• Failure of Rathke’s pouch craniopharyngeal ectoderm to differentiate into the adenohypophysis (the trophic hormone secreting section of the pituitary) results in a mucin filled Rathke’s cleft cyst in the sella turcica that is lined by ciliated pseudostratified columnar epithelium and goblet cells 
• Results in a deficiency or lack of all trophic hormones (functional panhypopituitarism or hyposomatotropism, depending on how much of the adenohypophysis fails to form) 
• Hyposomatotropism leads to deficiencies of the thyroid, adrenal gland, and gonadal hormones (low GH/IGF, TSH, prolactin, gonadotropins, +/- ACTH)

 

TYPICAL CLINICAL AND GROSS FINDINGS:

• Puppies are normal until approximately 2 months old, followed by:
  1. Subnormal growth (weighing as little as 2kg to half their normal weight as adults); appear “fox- or coyote-like”
  2. Retention of the wooly puppy hair coat and eventual hyperpigmentation 
  3. Bilaterally symmetric alopecia eventually leading to complete alopecia with only few tufts of hair on the legs and head
  4. Lack of estrus cycle
  5. Shortened lifespan 

 

TYPICAL GROSS FINDINGS:

• Lack of guard or primary hairs
• Thin, scaly skin, comedones, and bilaterally symmetric “endocrine” alopecia 
• Retention of puppy teeth 
• Slow closure of epiphyses up to four years 
• Infantile genitalia; hypoplastic ovaries and testicles

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Epidermis: hyperkeratosis, hyperpigmentation, atrophy 
• Hair follicles: follicular keratosis, hair shafts absent, hair follicles primarily in telogen (resting) phase, kenogen (hairless telogen) follicles, follicular atrophy, comedone formation 
• Dermis: loss of elastin fibers, loose arrangement of collagen fibers 
• Adnexal atrophy 

 

ADDITIONAL DIAGNOSTIC TESTS:  

 

DIFFERENTIAL DIAGNOSIS:

• Hypothyroidism (I-M22; congenital or acquired): No stunted growth or retention of puppy characteristics, but similar “endocrine” skin changes 
• Hyperestrogenism (I-M24): No stunted growth or retention of puppy characteristics, but similar “endocrine” skin changes
• Hyperadrenocorticism (I-M23): No stunted growth or retention of puppy characteristics, but similar “endocrine” skin changes; calcinosis cutis
• Acquired hypopituitarism secondary to neoplasia or inflammation

 

COMPARATIVE PATHOLOGY:

• Congenital hypopituitarism has been reported in cats and Eurasian badgers
• A recent case report in a Chihuahua (J Vet Diagn Invest, 2020) found similar signs (dwarfism, retained puppy coat, etc) secondary to a GH1 mutation causing low growth hormone with no detectable pituitary abnormalities and other endocrine hormones within normal limits. 

 

REFERENCES:

1. Iio A, Maeda S, Yonezawa T, et al. Isolated growth hormone deficiency in a Chihuahua with a GH1 mutation. J Vet Diagn Invest. 2020;32(5):733-736. 
2. Miller MA. Endocrine system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:780, 801.
3. Miller MA. Integumentary System. In: Maxie, MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier; 2016:589.
4. Rosol TJ, Gröne A. Endocrine Glands. In: Maxie, MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, PA: Elsevier; 2016:280-281.
5. Thaiwong T, Corner S, La Forge S, et al. Dwarfism in Tibetan terrier dogs with an LHX3 mutation. J Vet Diagn Invest. 2021;33(4):740-743.
6. Welle MM, Linder KE. The Integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1252.

 

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