We have studied the diurnal rhythm of pars distalis and pars intermedia-type immunoreactive (IR)-
POMC peptides and
cortisol in 3 normal dogs and 1 dog with
Cushing's syndrome and have documented the responses to a variety of agents in 42 dogs with
Cushing's disease, 2 of which were known or presumed to have pars intermedia
tumors and another of which had both pars distalis and pars intermedia
adenomas, and in 20 dogs with
adrenocortical adenomas causing
Cushing's syndrome. The normal dogs did not have a diurnal plasma
POMC peptide rhythm; the dog with
Cushing's disease appeared to have a similar number of secretory episodes of increased amplitude. Plasma
POMC peptides and
cortisol in animals with
Cushing's disease did not suppress normally with low dose
dexamethasone. Five animals with
Cushing's disease did suppress with high dose
dexamethasone, the dog with dual
adenomas suppressed only partially, and 1 dog with a pars intermedia
adenoma did not suppress at all. The response to
insulin-induced
hypoglycemia was similar in normal dogs and 4 dogs with
Cushing's disease, but 3 animals with adrenal
tumors did not respond. The response to
metyrapone was normal in 6 dogs with
Cushing's disease and, surprisingly, in 1 with adrenal
tumor.
Arginine vasopressin stimulated
POMC peptide secretion in normal and 6 Cushing's dogs, as well as
alpha MSH, a pars intermedia-type
POMC peptide, in a dog presumed to have a pars intermedia
tumor. Ovine CRF stimulated pars distalis-type
POMC peptide secretion in normal dogs and 17 dogs with
Cushing's disease, but not in 15 dogs with adrenal
tumor; IR-
alpha MSH was unaffected. TRH appeared to stimulate IR-
ACTH in normal animals, but not in those with
Cushing's disease.
Dopamine had no apparent effect in 2 normal and 1 Cushing's dogs. Initial plasma disappearance t1/2 values of IR-
ACTH and
lipotropin were 22-27 min. In summary, responses in normal and Cushing's dogs were generally what would be predicted from previous human and animal studies, but some of those in animals with pars intermedia
tumors and even in normal dogs were different from what had been anticipated. Canine
Cushing's syndrome provides an interesting model for an uncommon human disorder.