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Hypoadrenocorticism as the primary manifestation of lymphoma in two cats
Abstract
Hypoadrenocorticism secondary to bilateral lymphomatous invasion of adrenocortical tissue was diagnosed in 2 adult castrated domestic shorthair cats. In both cats, findings during initial physical examination (ie, lethargy, anorexia, weight loss, and severe weakness) were consistent with severe hypoadrenocorticism. Hyperkalemia, hyponatremia, and azotemia were also detected, which were consistent with hypoadrenocorticism. Hypoadrenocorticism was documented on the basis of finding low baseline and ACTH-stimulated serum cortisol concentrations. The cats initially responded well to treatment, but both owners chose to have the cat euthanatized. Multicentric lymphoma with infiltration and destruction of the adrenal glands was confirmed during necropsy.
... Hypoadrenocorticism in cats is uncommon, with approximately 40 cases described in the literature. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] The etiology of hypoadrenocorticism in dogs is believed to be immune-mediated lymphoplasmacytic inflammation and adrenocortical atrophy. Antibodies to adrenal cell antigens have been detected in 2 dogs with primary hypoadrenocorticism. ...
... Two cases of trauma-induced hypoadrenocorticism and 3 cases of primary adrenal lymphoma causing hypoadrenocorticism have been reported in cats. 2,5,6,16 Limited data is available on the ultrasonographic appearance of the adrenal glands in cats with primary hypoadrenocorticism. In the few cases in which the ultrasonographic appearance has been documented, the adrenal glands have been normal in size except for a case report in which the right adrenal gland could not be identified. ...
... 8,14,15,17 Adrenal insufficiency with adrenomegaly previously has been documented in cats only in the context of primary adrenal lymphoma. 2,16 In a study of 33 dogs with adrenalitis, inflammation was found to be lymphoplasmacytic in 17, lymphohistiocytic in 1, lymphocytic in 4, granulomatous in 3, and neutrophilic in 8. Adrenocortical atrophy Abbreviations: ACTH, adrenocorticotropic hormone; DOCP, desoxycorticosterone pivalate. was associated primarily with lymphoplasmacytic inflammation as opposed to non-lymphoid inflammation. ...
Case Description
An 18‐month‐old spayed female domestic short haired cat was presented for poor appetite, lethargy, exaggerated swallowing, and regurgitation 2 weeks after endoscopic retrieval of gastric foreign material.
Clinical Findings
The cat was quiet with tacky mucous membranes on physical examination. Point‐of‐care blood testing identified mild azotemia, moderate hypercalcemia, and a sodium‐to‐potassium ratio of 26. An ultrasound examination the next day identified moderate to marked bilateral adrenomegaly. Cytology of a fine needle aspirate of the adrenal glands was consistent with necrosis and associated inflammation. Hypoadrenocorticism was diagnosed by a confirmatory adrenocorticotropic hormone stimulation test.
Treatment and Outcome
The cat normalized both clinically and biochemically after treatment with prednisolone and desoxycorticosterone pivalate.
Clinical Relevance
Acute adrenal necrosis has been well documented in human medicine after anesthetic events. To our knowledge, hypoadrenocorticism caused by cytologically confirmed acute adrenal necrosis has not been previously reported in dogs and cats.
... Although the exact pathogenesis in this species is unknown, autoimmune destruction of the adrenal cortex is suspected in most cases, resulting in both glucocorticoid and mineralocorticoid deficiency. [74][75][76][77][78] The condition usually arises in middle-aged cats, although it has been reported in the young and elderly (8 months to 14 years). 77,[79][80][81][82][83][84][85][86] There is no known breed or sex predilection, [74][75][76][77][78][79][80][81]85,86 but most reports involve domestic shorthair and longhair cats. ...
... [74][75][76][77][78] The condition usually arises in middle-aged cats, although it has been reported in the young and elderly (8 months to 14 years). 77,[79][80][81][82][83][84][85][86] There is no known breed or sex predilection, [74][75][76][77][78][79][80][81]85,86 but most reports involve domestic shorthair and longhair cats. 6 Clinical signs appear to be similar to those in dogs, being non-specific and vague including anorexia, vomiting, lethargy and weight loss, which should respond to glucocorticoid therapy. ...
... There have also been three reported cases of hypoadrenocorticism in adult cats caused by bilateral lymphomatous adrenal infiltration. 76,78 In the most recent case, the authors describe bilateral and progressive adrenomegaly, the left gland reaching 2.4 x 2.6 x 2.9 cm in size and the right 2.8 x 2.6 x 2.8 cm. The glands were also reported to be abnormally hypoechoic and rounded with complete loss of normal architecture and were surrounded by mildly hyperechoic tissue. ...
Practical relevance
Abdominal ultrasound plays a vital role in the diagnostic work-up of many cats presenting to general and specialist practitioners. Ultrasound examination of the adrenal glands can provide important information pertaining to several conditions including hyperaldosteronism and hyperadrenocorticism.
Clinical challenges
Despite ultrasonography being a commonly used modality, many practitioners are not comfortable performing an ultrasound examination or interpreting the resulting images. Even for the experienced ultrasonographer, differentiating between incidental findings, such as adrenal mineralisation, and clinically significant pathological changes can be challenging.
Aim
This review, part of an occasional series on feline abdominal ultrasonography, discusses the ultrasonographic examination of the normal and diseased adrenal glands. Aimed at general practitioners who wish to improve their knowledge of and confidence in feline abdominal ultrasound, this review is accompanied by high-resolution images and videos available online as supplementary material.
Equipment
Ultrasound facilities are readily available to most practitioners, although the use of ultrasonography as a diagnostic tool is highly dependent on operator experience.
Evidence base
Information provided in this article is drawn from the published literature and the author’s own clinical experience.
... The use of IHC has previously confirmed a T-cell-rich pan-hypophysitis, consistent with autoimmune disease, in a cat with secondary hypoadrenocorticism. 15 Feline PH is also thought to occur secondary to autoimmune disease, resulting in a predominantly lymphocytic infiltration of the adrenal gland cortex, as recognised in dogs; however, neoplastic causes have also been documented. 4,16 In the two PH cases in which adrenal histopathology was previously reported and which were not associated with neoplasia, one had adrenal cortical size reduction, cortical replacement with fibrosis and diffuse lymphocytic infiltration extending into the medulla; the other had complete adrenocortical destruction and atrophy. 4,5 This is in comparison to cases secondary to adrenal lymphoma, in which mass lesions either encompassed or infiltrated the adrenal glands. ...
... 4,5 This is in comparison to cases secondary to adrenal lymphoma, in which mass lesions either encompassed or infiltrated the adrenal glands. 16 In humans with autoimmune hypoadrenocorticism, lymphoplasmacytic adrenalitis is typically seen; the lymphocytic population is predominantly T cells and is responsible for the adrenocortical cellular destruction. 17 Histopathological assessment in dogs with PH has also documented lymphoplasmacytic adrenalitis ± adrenocortical atrophy, with the predominant lymphocyte population being CD4 + T cells, consistent with the association of canine hypoadrenocorticism and major histocompatibility complex class II genes. ...
Case summary
A 6-year-old male neutered domestic longhair cat was referred for investigation of weight loss, hyporexia, vomiting and diarrhoea. The cat was diagnosed with primary hypoadrenocorticism, exocrine pancreatic insufficiency, cobalamin deficiency and a chronic enteropathy, and started on therapeutic treatment. Diabetes mellitus developed 4.5 months later, and the cat was started on insulin therapy. The cat was euthanased 10 months following the diagnosis of hypoadrenocorticism due to the development of status epilepticus, which was not associated with glucose or electrolyte abnormalities. Histopathological assessment of the adrenal glands at post-mortem examination documented lymphoplasmacytic adrenalitis, with the lymphocytic population being predominant. Immunohistochemical staining classified the lymphocytic infiltrate as T-cell rich, supportive of the cat’s hypoadrenocorticism being due to autoimmune disease.
Relevance and novel information
This case documents the novel use of immunohistochemical staining in combination with histopathology to further assess the adrenal glands in non-neoplastic-associated primary hypoadrenocorticism in a cat. This identified similar pathological changes to those previously described in dogs with autoimmune primary hypoadrenocorticism. Additionally, this is the first report of a cat with multiple endocrine disease that included primary hypoadrenocorticism and highlights that monitoring for the development of additional endocrine disease should be advised in these cases.
... Hypoadrenocorticism in cats is uncommonly reported in the veterinary literature, with most reports limited to 1 to 2 cases. [1][2][3][4][5][6][7] The 2 largest studies included small case numbers (10 and 11 cats), all of which had electrolyte abnormalities (hyponatremia or hyperkalemia or both). 4,5 To date, only 3 cases of cats with nonhyponatremic and nonhyperkalemic (NHNH) hypoadrenocorticism have been reported. ...
Background
Hypoadrenocorticism in cats is uncommonly reported. Most reports consist of cats with hyponatremia, hyperkalemia, or both.
Hypothesis/Objectives
To describe clinical findings, treatment response, and outcome in cats diagnosed with hypoadrenocorticism, including cats with abnormal and normal serum sodium and potassium concentrations.
Animals
Forty‐one cats with hypoadrenocorticism; 36 with and 5 without abnormal serum sodium and potassium concentrations.
Methods
Multicenter retrospective observational study. Data for the entire cohort were assessed using descriptive statistics and differences between cats with and without abnormal serum sodium and potassium concentrations were evaluated.
Results
Median age was 5.7 years (range, 0.2‐13.8). Twenty‐three (56%) cats were male and 18 (44%) were female. Cats with hyponatremia, hyperkalemia, or both were less likely to have a history of vomiting (P = .01) but more likely to be hypothermic (P = .03), dehydrated (P = .04) or weak (P = .04) on examination, compared with nonhyponatremic and nonhyperkalemic cats. Frequency of hypercalcemia was 31.7%. Exocrine pancreatic insufficiency (EPI) was diagnosed in 4/7 cats tested; all 4 had concurrent cobalamin deficiency. Thirty‐five (85.4%) cats survived to discharge. In 2 cats, hypoadrenocorticism occurred secondary to lymphoma. Median survival time (MST) for all‐cause mortality was 2035 days (95% confidence interval [CI], 294‐4380 days); MST for disease‐specific mortality was not reached.
Conclusions and Clinical Importance
Approximately one‐third of cats with hypoadrenocorticism had hypercalcemia. In some cases, hyponatremia and hyperkalemia were not observed. Cats with nonneoplastic associated hypoadrenocorticism that survive initial hospitalization can have a favorable long‐term prognosis. Testing for EPI may be warranted in cats with hypoadrenocorticism.
... 1,3,4,29 Adrenal cortex destruction and atrophy secondary to primary and metastatic lymphoma has been reported in two cats. 10 Two patients with trauma-induced hypoadrenocorticism have been described. 6,8 Adrenal insufficiency has also been reported in two kittens aged <12 months and congenital disease was hypothesised. ...
Practical relevance
Addison’s disease is a very rare condition in cats, with only approximately 40 cases documented in the past 40 years since it was first described in 1983.
Clinical challenges
While canine hypoadrenocorticism is a well-recognised disorder with clear diagnostic and treatment guidelines, feline hypoadrenocorticism remains a challenge because of its rarity and waxing and waning clinical signs. Furthermore, empirical treatment with corticosteroids, resulting in clinical improvement, contributes to delays in achieving the diagnosis and initiating treatment. Feline hypoadrenocorticism is diagnosed with an adrenocorticotropic hormone (ACTH) stimulation test; a low resting cortisol concentration with an inadequate or absent response to synthetic ACTH is diagnostic. Various ACTH stimulation-testing protocols are reported in published cases, with the majority using three time-limited blood samples. This can be limiting clinically, depending on cats’ clinical presentation and behaviour at the veterinary practice and tolerance for procedures. Long-term treatment, similar to canine hypoadrenocorticism, consists of oral corticosteroids, with several formulations licensed in the UK, and mineralocorticoids (desoxycorticosterone pivalate), of which the only available formulation (Zycortal; Dechra) is licensed for dogs and its safety has not been assessed in cats.
Global importance
Feline hypoadrenocorticism occurs worldwide. Although no breed, sex or age association has been reported, cats aged <6 years are overrepresented.
... Hypoglycemia has also been reported in cats with hypoadrenocorticism, and in relation to cortisol secretion disorders in the adrenal gland, it may be caused by a decrease in glycogenolysis and gluconeogenesis in the liver. However, glucose levels were above the normal range in this cat (8,14). In previous reports on cats diagnosed with hypoadrenocorticism, hepatic transaminase levels, including aspartate aminotransferase, were increased in only one case, and the aspartate aminotransferase levels were also slightly increased in this cat (8,17). ...
A 7 wk old female spayed domestic shorthair was evaluated for 3 days of lethargy and anorexia 1 wk after ovariohysterectomy. On presentation, she was weak, dehydrated, and hypotensive. Blood work showed azotemia, hyponatremia, hyperkalemia, hyperphosphatemia, and hyperproteinemia. Ingestion of a nephrotoxic substance was unlikely, there was no evidence of infection on urinalysis, and an abdominal ultrasound showed normal renal architecture with no evidence of ureteral ligation. A diagnosis of hypoadrenocorticism was established based on low baseline cortisol and aldosterone concentrations and lack of response to synthetic adrenocorticotropic hormone administration. Treatment was initiated with IV fluid therapy, corticosteroids, and subcutaneous desoxycorticosterone pivalate. After 3 mo of treatment, the cat continued to do clinically well with a decreasing dose of glucocorticoids. Owing to owner concerns with frequent veterinary visits and medication cost, the decision was made to extend the mineralocorticoid dose interval while closely monitoring clinical status and electrolyte concentrations. The cat’s electrolytes remained normal and medications were discontinued. Repeat baseline cortisol and aldosterone concentrations and response to adrenocorticotropic hormone administration 18 days after discontinuing all medication revealed that adrenal function had recovered. This is the first report of transient hypoadrenocorticism in this species.
Ce cas illustre le diagnostic d’une maladie d’Addison chez un chat femelle stérilisée Scottish fold de 4,5 ans présentant un historique de dysorexie, d’abattement et d’amaigrissement évoluant depuis un mois dans un contexte d’azotémie et de diminution du rapport Na/K persistantes. L’hypocorticisme primaire est confirmé par une valeur d’ACTH (hormone adrénocorticotrope) endogène augmentée ainsi qu’un test de stimulation à l’ACTH documentant un hypocortisolisme et un hypoaldostéronisme. La prise en charge thérapeutique constituée d’une supplémentation en prednisolone et en DOCP (pivalate de désoxycortone) permet une amélioration des signes cliniques et des anomalies biologiques en moins de 5 jours. Ce cas illustre le défi diagnostique de l’hypocorticisme, très rarement rencontré chez le chat et mimant parfois des maladies beaucoup plus fréquentes dans cette espèce. Enfin, ce cas montre que le DOCP peut être utilisé avec succès en tant que supplémentation en minéralocorticoïdes lors de maladie d’Addison chez le chat.
The aim of this study was to assess the effects of commonly used anaesthetics alfaxalone and propofol on salivary and urinary cortisol in healthy cats. Fifteen male castrated research-purposed cats received randomly intravenous continuous rate infusions of 8 mg/kg/h of alfaxalone, 12 mg/kg/h of propofol and 2 ml/kg/h of Lactated Ringer's solution for 30 min, with intervals of 6 days between treatments. Saliva samples were collected for 24 h before each infusion and for 24 h from the start of each infusion. Urine was collected as single pooled samples over each 24 h period. Mean integrated saliva cortisol responses in cats treated with alfaxalone were greater than responses of cats treated with propofol (P = 0.034) and controls (P = 0.017). Integrated responses in cats treated with propofol did not differ from controls. The mean urinary cortisol/creatinine ratio (UCCR) was higher on the day of treatment than the day before treatment in cats treated with alfaxalone (P < 0.0001) and in cats treated with propofol (P = 0.0168) and did not differ between days in cats treated with lactated Ringer's solution. The mean UCCR was higher in cats treated with alfaxalone than in cats treated with lactated Ringer's solution (P = 0.0020) on the day of treatment. Mean total urinary cortisol over 24 h was greater in cats treated with alfaxalone than controls (P = 0.0267). In conclusion, alfaxalone increased short-term salivary and urinary cortisol concentrations in healthy cats as compared to propofol and a control group of non-anesthetised cats.
Plasma cortisol and immunoreactive (IR)-ACTH responses to 125 micrograms of synthetic ACTH (cosyntropin) administered IV or IM were compared in 10 clinically normal cats. After IM administration of cosyntropin, mean plasma cortisol concentration increased significantly (P less than 0.05) within 15 minutes, reached maximal concentration at 45 minutes, and decreased to values not significantly different from baseline concentration by 2 hours. After IV administration of cosyntropin, mean plasma cortisol concentration also increased significantly (P less than 0.05) at 15 minutes, but in contrast to IM administration, the maximal cortisol response took longer (75 minutes) and cortisol concentration remained significantly (P less than 0.05) higher than baseline cortisol concentration for 4 hours. Mean peak cortisol concentration (298 nmol/L) after IV administration of cosyntropin was significantly (P less than 0.05) higher than the peak value (248 nmol/L) after IM administration. All individual peak plasma cortisol concentrations and areas under the plasma cortisol response curve were significantly (P less than 0.05) higher after IV administration of cosyntropin than after IM administration. Mean plasma IR-ACTH concentration returned to values not statistically different from baseline by 60 minutes after IM administration of cosyntropin, whereas IR-ACTH concentration still was higher than baseline concentration 6 hours after IV administration. Peak plasma IR-ACTH concentration and area under the plasma IR-ACTH response curve also were significantly (P less than 0.05) higher after IV administration of cosyntropin. Results of the study confirmed that IV administration of cosyntropin induces significantly (P less than 0.05) greater and more prolonged adrenocortical stimulation than does IM administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypoadrenocorticism (also known as Addison's disease, adrenal insufficiency, or adrenocortical hypofunction) is often called the great pretender because the associated clinical signs can mimic those of other diseases. Primary hypoadrenocorticism is a direct failure of the adrenal glands to produce physiologically adequate amounts of glucocorticoids, mineralocorticoids, or both. In secondary hypoadrenocorticism, decreased secretion of corticotropin in the pituitary or corticotropin-releasing hormone by the hypothalamus can lead to decreased production of glucocorticoids. About 70% of affected dogs are female. The average age at diagnosis is about 5 years. Breeds at risk for developing the disease include the Great Dane, poodle, and West Highland white terrier; the Lhasa Apso and Yorkshire terrier are at lower risk. Clinical signs include vomiting, anorexia, weakness, lethargy, weight loss, diarrhea, and dehydration. Laboratory findings include hyponatremia, hyperkalemia, and a decreased serum:potassium ratio. Affected dogs are more likely than is the general canine population to have anemia or hypothyroidism. Emergency treatment of hypoadrenocorticism deals with patient stabilization; maintenance treatment includes administration of glucocorticoids and mineralocorticoids to reestablish physiologic homeostasis. Dogs with primary disease may require replacement of either or both, whereas dogs with secondary disease usually require glucocorticoids but not replacement of mineralocorticoids.
We report an unusual case of Addison's disease which is unique in being diagnosed ante-mortem as being due to Non-Hodgkin's lymphoma of the adrenal glands. Both ante- and post-mortem examinations showed the lymphoma to be entirely confined to the adrenals.
Four normal cats were treated weekly for 4 weeks with repositol methylprednisolone. Hemograms, serum chemistry panels, urinalyses, 24 hour water consumption, physical and constitutional parameters, and blood cortisol responses to ACTH stimulation were monitored before and during a day were done prior to steroid therapy on each cat. Clinicopathologic abnormalities induced by steroid therapy were, on the whole, inconsistent and minor. The most important findings were: (1) marked steroid-induced suppression of blood cortisol responses to ACTH, and (2) a circadian rhythm of blood cortisol production that was opposite to that of humans and dogs.
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The adrenal gland is not uncommonly involved in lymphoma. It is rare, however, for adrenal lymphoma to present as Addison's disease. There are only eight reports in the English literature. This paper reports a case of adrenal lymphoma that presented with Addison's disease and hypercalcaemia.
Angiotropic large-cell lymphoma is a rare disorder characterized by a proliferation of malignant lymphoid cells within the lumina of small vessels. The skin and central nervous system are typically affected; however, involvement of other organs has been described. We document an unusual case of this disorder in a patient who suffered clinically significant adrenal insufficiency and subsequently died. Autopsy disclosed angiotropic large-cell lymphoma involving both adrenal glands.
A case of non-Hodgkin's lymphoma (large cell immunoblastic sarcoma) arising as a primary malignancy in the adrenal gland is reported and the literature concerning this unusual tumor is reviewed. Although extremely rare, it is possible to make the diagnosis preoperatively. Therefore, primary adrenal lymphoma should be included in the differential diagnosis of a suprarenal mass.
A 73-year-old woman who presented with primary adrenal insufficiency and enlarged adrenal glands on computed tomographic scanning was ultimately found to have a large-cell lymphoma that had initially involved the adrenals and the stomach. A search of the English language medical literature revealed only seven other cases of lymphoma presenting with hypoadrenalism, none of which involved the stomach. As in this case, in most of those cases adrenal enlargement was documented on computed tomographic scanning. Despite its rare occurrence, lymphoma should be searched for in patients presenting with Addison's disease and enlarged adrenal glands.