Central Diabetes Insipidus in a Dog With a Pro-Opiomelanocortin-Producing Pituitary Tumor ot Causing Hyperadrenocorticism

Central Diabetes Insipidus in a Dog With a Pro-Opiomelanocortin-Producing Pituitary Tumor N o t Causing Hyperadrenocorticism Marielle M.C. Goossens, Ad Rijnberk, Jan A. Mol, Jeannette Wolfswinkel, and George Voorhout Central diabetes insipidus was diagnosed by vasopressin measurements during hypertonic stimulation in a O-yearold male giant Schnauzer with polyuria and polydipsia. The impaired release of vasopressin was believed to be caused by a large pituitary tumor, which was visualized by computed tomography. Studies of the function of the anterior lobe and the pars intermedia of the pituitary gland were conducted, and high concentrations of ACTH and a-melanotrophic hormone (a-MSH) were found without concomitant hyperadrenocorticism. Studies of the molecular size of

the immunoreactive ACTH in plasma by gel filtration revealed that most of the circulating immunoreactivity was not ACTH but its precursor pro-opiomelanocortin (POMC) and low-molecular-weight POMC-derived peptides. The pituitary tumor of this dog probably originated from melanotrophic cells of the pars intermedia. The sensitivityof the pituitary-adrenocortical system for the suppressive effect of dexamethasone was unaffected. J Vetlntern Med 1995;9:361-365.Copyright0 1995by the American College of Veterinary InternalMedicine.

ntral diabetes insipidus (CDI) results from failure of the neurohypophyseal system to produce or release sufficient vasopressin for normal renal water conservation. The condition may be complete or partial, permanent or temporary, and usually is characterized by production of large volumes of hypotonic urine. Pituitary neoplasia is a common cause of impaired vasopressin release in middle-aged and older dogs. In older dogs, the diagnosis may be complicatedbecause of the frequent occurrence of hyperadrenocorticism. In hyperadrenocorticism,glucocorticoid excess interferes with the action of vasopressin in the kidney and results in disturbances in the osmoregulation of vasopressin release. In addition, the pituitary lesion in pituitary-dependent hyperadrenocorticism (often an adenoma) may cause neurohypophyseal dysfunction by expansion.' These ACTH-producing adenomas may originate from corticotrophic cells in the anterior lobe of the pituitary gland. Adenomas also may arise from melanotrophic (A) or corticotrophic (B) cells of the pars intermedia (PI). These cells produce a-melanocytestimulating hormone (a-MSH) and ACTH, respectively, with a-MSH resulting from further processing of the precursor molecule, pro-opiomelanocortin (POMC).3-5 In this report, we describe a dog with CDI and a pituitary tumor releasing POMC and POMC-derived peptides, but not causing h yperadrenocorticism.

(growth hormone [GH], ACTH) and the pars intermedia (a-MSH, ACTH, POMC). While awaiting the results of these studies, the dog was treated with desmopressin acetate (DDAVP), a synthetic vasopressin analogue (Minrin; Femng BV, Haarlem, The Netherlands), in adose of 1 drop in the conjunctival sac tid. Water intake returned to normal during this treatment. For financial reasons, the owner often administered the DDAVP only bid. Although this was associated with some increase in water intake and urine production, it was still satisfactory to the owner. The dog did well for 15 months and was then euthanized by the referring veterinarian for reasons not clearly related to the polyuria. Necropsy was not performed.

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Methods

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The osmoregulation of vasopressin release was investigatedby IV infusion of 20% NaCl for 2 hours at a rate of 0.03 mL/minute/kg BW. Samplesfor measurementsof plasma vasopressin (PAVP) and plasma osmolality (POSM) were obtained at 20-minute intervals. This allowed PAVP concentrations to be expressed as a function of increasing POSM. The data thus obtained were compared with those in healthy dogs, for which a nomogram has been compiled.8 The study was conducted after the dog had been fasted for 12 hours. Plasma samples were handled as described elsewhere.2 PAVP was measured by radioimmunoassaywith '*'I-AVP as the tracer and a second antibody for the separation of the bound and free tracer, as described elsewhere? The detection limit of the assay was 0.5 pmol/L. The plasma concentrations ofACTH, cortisol, and a-MSH were measured before and after the administration of dexamethasone at a dose of 0.01 mg/kg BW IV (low-dose dexamethasone suppression test [LDDST]) and at a dose of 0.1 mg/kg BW IV (high-dosedexamethasonesuppression test [HDDST])? Plasma

A 9-year-old male giant Schnauzer was presented for polyuria and polydipsia of 8 months duration, without other clinical signs. There were no abnormalities on physical examination. Common causes of polyuria and polydipsia were excluded by physical examination and evaluation of clinical chemistry results (Table 1). Hyperadrenocorticism was excluded by measuring urinary corticoid/ creatinine(C/C) ratios. In 6 measurements,the ratio varied between (reference range