A 20-yr-old nulliparous female lowland gorilla had developed severe truncal obesity over the course of 2 yr.
This animal lived with a troop consisting of 2.2 conspecifics; an adult male was removed from the group in early 1997. Prior to
this time this animal's medical history consisted of irregular menstrual cycle, polyuria, and hyperphagia actually contributing to
social conflicts with other troop members. The female gorilla had a behavioral history of hair plucking that extended back to her
previous facility 9 yr previously. In June 1998 she experienced a bout of lethargy and a fractured the right central incisor.
During a cursory visual exam for that problem a petit mal seizure was witnessed wherein her eyes rolled back into her head, she
slumped over, and she was non-responsive to tactile or auditory stimuli for about 45 sec. She was semi-catatonic and reluctant to
use her right hand in the immediate post-ictal phase, but by late in the day was back to normal. The next morning she was found
with wide bands of skin excoriations around her abdomen and right flank, and on her back. At this time all the skin lesions were
localized to the right. Medial deviation of her left eye was also noted.
Several attempts were made to culture skin wounds, perform skin scrapes and treat the skin wounds with topical
and systemic medications including antibiotics, astringents, and anti-histamines. No specific etiology could be gathered from these
diagnostics and therapeutics, and the lesions grew as a result of self plucking. Urinary cortisol:creatinine ratios (UCCR) from
this female suggested that the pituitary-adrenal axis warranted closer examination. A differential diagnosis list to include all of
her findings at this point centered around hormonal dysfunction and included polycystic ovarian syndrome, hyperadrenocorticalism,
hyperthyroidism, and possibly others endocrinopathies, such as acromegaly and hyperprolactinemia. A physical examination under
general anesthesia 9 mo later included a general physical examination, a dermatology consultation, reproductive evaluation, and
magnetic resonance imaging (MRI) of the skull. The physical examination revealed a grossly obese animal with the fat distributed
primarily in the trunk and the back of the neck, severe bruises on the arm, and generalized muscle atrophy of the limbs.
Diagnostics of the skin included biopsy for histopathology, bacterial, fungal, and viral culture. The histologic diagnosis was
dermal fibrosis and a mild amount of Staphylococcus aureus was grown on culture. The reproductive exam was not informative.
MRI with gadolinium contrast delivered i.v. demonstrated a 2.5-mm mass consistent with a microadenoma on the right side of the
anterior pituitary. Serum biochemistry abnormalities were mild and consisted of hypocalcemia, hypernatremia, hyperkalemia,
hyperchloremia, hyperlipasemia, and elevated testosterone. Based on the history, clinical signs and this examination, a tentative
diagnosis of pituitary dependent hyperadrenocorticalism (Cushing's disease) was made.
During the next several months, many consultations were made with endocrinologists, neurologists, and
neurosurgeons regarding this case. The presence of a presumptive pituitary lesion warranted investigation of the hormonal status of
the adrenal gland. A low dose dexamethasone suppression test using urinary cortisol analysis was elected to evaluate the status of
the pituitary B adrenal axis. This animal and a 31-yr-old female gorilla were given dexamethasone (1 mg p.o.) at midnight and all
voided urine collected from a clean cafeteria tray at 0800 hr the next morning. Because the test animal suppressed to the same
levels as the control, the possibility of Cushing's syndrome/disease (CD) seemed less likely. In November 1999, a follow-up
examination was performed to specifically evaluate the reproductive status of this female. A corticotrophin stimulation test, 100
µg i.v. corticorelin ovine triflutate (ActhrelTM, Ben Venue Laboratories, Bedford, OH 44146 USA) was performed to
rule out any possibility of hyperadrenalcorticalism. Transrectal ultrasonography examination exam revealed several small hypoechoic
areas on the right ovary consistent with polycystic ovarian syndrome. The cervix had a moderate amount of mucosal congestion.
Anesthesia was unremarkable until upon recovery, the gorilla became comatose and was placed on a ventilator overnight. Twelve hours
into recovery her neurologic status became questionable and was in severe respiratory acidosis. Electrocardiogram tracings, peaked
T waves, wide QRS complexes, and flattened P waves, suggested hyperkalemia. An electroencephalogram detected some very low
amplitude activity but the animal expired shortly after the examination.
Gross necropsy revealed an obese gorilla with a truncal distribution of fat and little fat in the subcutaneous
tissue of any limb. A large amount of fat was found in the thoracic cavity overlying the lung fields. The pituitary gland was
swollen out of the sella dorsally. Several small tags of endometrial tissue were found in the abdomen on the serosal surface of the
right side of the uterus. There was multifocal chronic active ulceration in the distal esophagus and stomach. The left adrenal was
approximately three times normal size and had a severely necrotic center. The right adrenal could not be found. On histologic
examination the left adrenal was necrotic and the pituitary demonstrated diffuse hyperplasia. Results of follicle stimulating
hormone (FSH), luteinizing hormone (LH), thyrotropin stimulating hormone (TSH), growth hormone (GH), and adrenal-corticotrophin
hormone (ACTH), prolactin staining are pending at the time of this writing. The corticotrophin stimulation test revealed a
hyperresponsive elevation of plasma ACTH and serum cortisol levels that remained near baseline.
While clinical diagnosis and imaging modalities are extremely useful in the overall diagnosis and treatment
plans for CD, laboratory confirmation is the hallmark of making a definitive diagnosis.6 Urinary cortisol:creatinine
ratios (UCCR) have been utilized in ferrets,5 humans,3 and to some degree in dogs1,4 in an effort
to diagnose hyperadrenocorticalism. Morning collections from all members of this gorilla troop showed elevations of UCCR
(institutional normals = 25-45, n = 6 individuals), but this female had consistently elevated levels (50-65, institutional
normals < 14, n = 6 individuals) at evening collections. This finding is not definitive for CD but does suggest some loss
to a diurnal cycle in the affected female gorilla compared to the others. Another possibility for the lack of clinicopathologic
support for clinical CD by UCCR values in this animal may have been related to progressive adrenal gland necrosis such that
cortisol was falling into the normal range, as the animal was experiencing hyperadrenalcorticalism (Addison's disease). This theory
may explain why suppression was noted after administration of p.o. low dose dexamethasone. The results of the corticotrophin
stimulation also support this theory and are consistent with those of patients with Addison's disease. Macronodular adrenal
hyperplasia also allows failure to suppress at a low dose in suspect clinical CD. Bilateral6 and unilateral2
hyperplasia have been reported in cases of chronic CD patients. The literature remains unclear whether the adrenal gland is
responding to the pituitary stimulation or the adrenal gland is the primary problem. Familiar CD has been documented in humans but
has not yet been pursued with this gorilla. The relationship between the seizure activity and CD is unclear still but steroid
psychosis in chronic CD is not uncommon6 and may explain her tritrichomania and some other aberrant behaviors.
1. Angles JM, EC Feldman, RW Nelson, MS Feldman. 1997. Use of urine cortisol:creatinine ratio versus
adrenocorticotropic hormone stimulation testing for monitoring mitotane treatment of pituitary-dependent hyperadrenocorticism in
dogs. J. Am. Vet. Med. Assoc. 211:1002-1004.
2. Bunch FT, BA Warner. 1993. Cushing's disease with a unilateral adrenal macronodule: evolutive
transition or incidental finding? South. Med. J. 86: 235-238.
3. Corcuff JB, A Tabarin, M Rashedi, M Duclos, P Roger, D Ducassou. 1998. Overnight urinary free
cortisol determination: a screening test for the diagnosis of Cushing's syndrome. Clin. Endocrinol. (Oxf) 48: 503-508.
4. Galac S, HS Kooistra, E Teske, A Rijnberk. 1997. Urinary corticoid/creatinine ratios in the
differentiation between pituitary-dependent hyperadrenocorticism and hyperadrenocorticism due to adrenocortical tumour in the dog.
Vet. Q. 19: 17-20.
5. Gould WJ, TJ Reimers, JA Bell, HJ Lawrence, JF Randolph, PH Rowland, JM Scarlett. 1995. Evaluation
of urinary cortisol:creatinine ratios for the diagnosis of hyperadrenocorticism associated with adrenal gland tumors in ferrets.
J. Am. Vet. Med. Assoc. 206: 42-46.
6. Orth DN. 1995. Cushing's syndrome. N. Engl. J. Med. 332: 791-803.