Acromegaly

From Dog
A 10-year-old intact female Miniature Dachshund with weight gain, facial enlargement and acromegaly due to multiple mammary tumors[1]

Acromegaly (hypersomatotropism) is an endocrine disorder characterized by progestin-induced hypersecretion of growth hormone (GH) by mammary hyperplasia, with resultant overgrowth of the soft tissue, bone, and viscera.

In humans and cats, acromegaly is commonly caused by pituitary adenomas producing GH[2][3].

Rare cases of pituitary adenomas resulting in acromegaly have been reported in dogs[4], but acromegaly is usually caused by GH production at hyperplastic mammary glands or mammary adenocarcinoma[5][6]. Although GH is also produced by mammary tumors in dogs, there has been no report with clinically obvious acromegaly induced by GH-producing mammary tumors[7].

Excess growth hormone invariably results in insulin resistance at the hepatic and muscular level, resulting in heightened insulin production[8]. GH production by the mammary gland is not unique to the dog and has been reported in cats. Locally produced GH within the hyperplastic ductular epithelium of the mammary gland not only plays a role in the morphologic changes of the mammary gland associated with the ovarian cycle and gestation, but is also involved in the development of mammary neoplasia[9].

Clinically affected dogs present with visible mammary expansion, polyuria, polydipsia, polyphagia, weight gain, facial and limb muscle and skin hypertrophy and inspiratory stridor[1]. Transient diabetes insipidus has been reported during estrus in bitches with acromegaly[10].

A history of progestin use (e.g. proligestone) may preclude development of mammary hyperplasia and initiate onset of acromegaly[11].

Routine blood tests and abdominal imaging are frequently within normal limits.

Diagnosis is usually based tentatively on clinical signs and demonstration of elevated serum growth hormone (normal 0.5 – 3 ng/ml), insulin (normal 7.0 – 17.0 μU/ml) and insulin-like growth factor-I (normal 72.1 – 165.0 ng/ml) levels. This must be interpreted in the light of pulsatile secretion pattern of GH changes during the luteal phase of the canine reproductive cycles, with basal GH secretion being higher and pulsatile GH secretion being lower when plasma progesterone concentration is high[12].

Testing of circulating total thyroxine, free thyroxine, TSH and an ACTH stimulation test are recommended to eliminate other endocrine diseases[4].

A differential diagnosis would include other auses of polyuria, including gestational diabetes[13], diabetes insipidus, and hypoadrenocorticism and other causes of elevated GH such as hypothyroidism[14].

In entire bitches, ovariohysterectomy and mastectomy is usually curative.

Drugs such as aglepristone have also shown to be effective at resolution of clinical symptoms[15].

References

  1. 1.0 1.1 Murai A et al (2012) GH-producing mammary tumors in two dogs with acromegaly. J Vet Med Sci 74(6):771-774
  2. Nabarro, JD (1987) Acromegaly. Clin Endocrinol (Oxf) 26:481–512
  3. Niessen, SJ (2010) Feline acromegaly: an essential differential diagnosis for the difficult diabetic. J Feline Med Surg 12:15–23
  4. 4.0 4.1 Fracassi F et al (2007) Acromegaly due to a somatroph adenoma in a dog. Domest Anim Endocrinol 32(1):43-54
  5. Rijnberk, A & Mol, JA (1997) Progestin-induced hypersecretion of growth hormone: an introductory review. J Reprod Fertil Suppl 51:335–338
  6. Selman, PJ et al (1994) Progestin-induced growth hormone excess in the dog originates in the mammary gland. Endocrinology 134:287–292
  7. van Garderen, E et al (1997) Expression of growth hormone in canine mammary tissue and mammary tumors. Evidence for a potential autocrine/paracrine stimulatory loop. Am J Pathol 150:1037–1047
  8. Jørgensen JO et al (2002) Somatropin and glucose homeostasis: considerations for patient management. Treat Endocrinol 1(4):229-234
  9. Rijnberk A et al (2003) Endocrine diseases in dogs and cats: similarities and differences with endocrine diseases in humans. Growth Horm IGF Res 13(A):S158-S164
  10. Schwedes CS (1999) Transient diabetes insipidus in a dog with acromegaly. J Small Anim Pract 40(8):392-396
  11. Knottenbelt CM & Herrtage ME (2002) Use of proligestone in the management of three German shepherd dogs with pituitary dwarfism. J Small Anim Pract 43(4):164-170
  12. Kooistra HS & Okkens AC (2002) Secretion of growth hormone and prolactin during progression of the luteal phase in healthy dogs: a review. Mol Cell Endocrinol 197(1-2):167-172
  13. Norman EJ et al (2006) Pregnancy-related diabetes mellitus in two dogs. N Z Vet J 54(6):360-364
  14. Lee WM et al (2001) Primary hypothyroidism in dogs is associated with elevated GH release. J Endocrinol 168(1):59-66
  15. Bhatti SF et al (2006) Treatment of growth hormone excess in dogs with the progesterone receptor antagonist aglépristone. Theriogenology 66(4):797-803