Unlike the situation in humans and cats, acromegaly in the dog due to a pituitary adenoma is extremely rare, although a case has been described. Acromegaly in the dog is more frequently related to the production of mammary growth hormone (GH). This production occurs in middle-aged or elderly bitches during the luteal phase of the oestrous cycle as a consequence of high levels of progesterone in the blood or as the result of treatment with progestins.
In the luteal phase, as in pregnancy, plasma concentrations of progesterone are raised. The values start from 5-25 ng/ml in the first half of dioestrus, reaching levels as high as 50-90 ng/ml in some subjects, compared with concentrations below 2 ng/ml before the luteinising hormone peak.
The high concentrations of progesterone in the plasma during the luteal phase induce secretion of GH from foci of hyperplastic columnar epithelium in the breast. The high levels of GH induced by the hyperprogesteronaemia can lead to acromegaly, particularly in elderly bitches during dioestrus, when the synthesis of progesterone is maximal.
This condition has also been recently described in two pregnant bitches; the concentrations of progesterone during pregnancy are the same as those during the metoestrus. The administration of synthetic progestins can also lead to an excess of GH, causing the signs of acromegaly. There are reports in the literature of dogs with pituitary tumours potentially responsible for excessive amounts of GH but the first documented case of over-secretion of GH caused by a somatroph adenoma in a Dalmatian dog with acromegaly was published only recently (Figs. 1 and 2).
CLINICAL SIGNS
The signs and symptoms of excess secretion of GH tend to develop gradually and are related to the increased body size of the animal. There is obvious excessive growth of soft tissues of the head with enlargement of the tongue and pharynx to the point of causing respiratory stridor; the interdental spaces are often widened.
In the single documented case of a dog with acromegaly caused by a pituitary tumour, the patient also had signs of progressive stiffness during walking with difficulty in maintaining a standing position, intolerance of neck manipulation because of proliferation of joint cartilage, and severe spondylosis deformans with osteophytes.
With regards to effects on the skin, various degrees of hyperkeratosis and hyperplasia of the epidermis and dermis, sometimes associated with a certain amount of hypertrichosis, have been described. Dermal hyperplasia is caused by increased production of collagen, an increase in fibroblasts and accumulation of mucopolysaccharides, which give the tissues a dense, compact and thickened appearance, and can be associated with diffuse mucinous degeneration (myxoedema).
The signs and symptoms of canine acromegaly due to an excess of mammary GH are the same as those of acromegaly of pituitary origin; the symptoms initially tend to regress following the metoestrus, however, they become ever more severe with successive oestrous cycles. The mildest forms and earliest stages of the disease are usually characterized by polyuria, polydypsia, sometimes polyphagia, noisy breathing and asthenia.
LABORATORY TESTS
Dogs with acromegaly often also have hyperglycaemia, increased levels of plasma alkaline phosphatase, liver enzymes, and phosphate, and urine with a low specific gravity. The only reported case of a dog with acromegaly due to a GH-secreting pituitary adenoma also had mild anaemia and increased levels of creatine kinase, cholesterol and fructosamine.
DIAGNOSIS
The diagnosis of excess GH is dependent on the presence of the characteristic clinical signs or a history of prolonged administration of progestins. When the diagnostic suspicion is strong, hormonal assays can be used, including the measurement of plasma levels of GH and insulin-like growth factor I (IGF-I).
GH assays are not without problems; in fact, a high level of GH in the plasma may be the result of secretory pulse in a healthy animal. It is, therefore, recommended that three to five samples of blood are collected at intervals of 10 minutes for the GH assay. In a study of a group of bitches with spontaneous acromegaly and progestin-induced acromegaly, the concentrations of GH ranged from 11 to 1476 ng/ml.
It is extremely useful to measure the levels of IGF-I because these are much less subject to fluctuations, given that IGF-I is bound to transport proteins. The size and age of the animal should be taken into consideration, since IGF-I levels are directly proportional to the subject’s mass and age.
The lack of suppression of GH after a glucose tolerance test and after a somatostatin suppression test support a suspected diagnosis of acromegaly.
Measurement of the levels of thyroid hormones can be important in order to exclude primary hypothyroidism which sometimes produces similar clinical signs. Care must, however, be taken because decreased levels of thyroid hormones may be related to euthyroid sick syndrome.
Subjects with progestin-induced acromegaly may have suppressed secretion of ACTH with consequent adrenal insufficiency secondary to the intrinsic glucocorticoid-like activity of progestins.
In the Dalmatian dog with acromegaly of pituitary origin, computed tomography showed the increased volume of the pituitary gland and a small pituitary cystic structure with a diameter of about 1.5 mm.
| Glucose tolerance test | Somatostatin suppression test | |
| The levels of glucose and insulin in the blood are measured at time 0 and 15, 30, 60 and 90 minutes after intravenous administration of 1g/kg glucose 50%. Subjects with acromegaly do not tolerate the glucose load, and after its administration develop hyperinsulinism and altered insulin responses. The high basal concentrations of insulin found in acromegalic subjects develops to compensate for the increased levels of glucose; in fact, in the early stages of acromegaly high levels of insulin can be found together with normoglycaemia or modest hyperglycaemia. Furthermore, after administration of glucose, the concentration of GH does not decrease, at variance to what happens in healthy subjects. | Serum concentrations of GH are measured 15 minutes before the intravenous administration of 10 µg/kg of somatostatin, at the time of the administration (time 0), and 15, 30, 45, 60 and 90 minutes after its administration. In healthy subjects somatostatin inhibits the synthesis of GH; in contrast, in subjects with acromegaly, GH values are not lowered by the inhibitory effect of the somatostatin. |
TREATMENT
Acromegaly induced by progestins can be managed by withdrawal of the hormone treatment and/or ovariectomy/ovariohysterectomy. This causes a reduction in the volume of soft tissues, in particular those of the oropharynx, and in abdominal volume. In contrast, the bone changes are irreversible. In the case in which the excess of GH has not led to complete exhaustion of the pancreatic β cells, the elimination of the endogenous or exogenous source of progestogens can prevent the development of persistent diabetes mellitus. It must be appreciated that the effect of progestins can last for several months; for this reason, the administration of progesterone-receptor blockers (es. aglipristone) could be useful in animals which have recently started progestin therapy, although further studies documenting the efficacy of such products are needed.
PROGNOSIS
The prognosis of progestin-induced acromegaly is good with regards to all the potentially reversible symptoms except the development of diabetes mellitus which may not regress.
Suggested readings
- Feldman EC, Nelson RW. Disorders of growth hormone. In: Canine and Feline Endocrinology and Reproduction. 3rd edition. Saunders, St. Louis, Missouri, 2004;45-84.
- Fracassi F, Gandini G, Diana A, et al. Acromegaly due to a somatotroph adenoma in a dog. Domest Anim Endocrinol 2007;32:43-54.
- Meij BP, Kooistra HS, Rijnberk A. Hypothalamus-pituitary system. In: A Clinical Endocrinology of Dogs and Cats. Eds. Rijnberk A, Kooistra HS. Schlutersche, Hannover, 2010;13-54.
- Rijnberk AD, Kooistra HS, Mol JA. Endocrine disease in dogs and cats: similarities and differences with endocrine disease in humans. Growth Hormone & IGF Research 2003;13:158-64.
- Van Keulen LJ, Wesdorp JL, Kooistra HS. Diabetes mellitus in a dog with a growth hormone-producing acidophilic adenoma of the adenohypophysis: Vet Pathol 1996;33:451-3.