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Pretreatment clinical and laboratory findings in dogs with hypoadrenocorticism
Abstract
To evaluate clinical and laboratory findings in 225 dogs with naturally occurring hypoadrenocorticism diagnosed over a 14-year period.
Retrospective case series.
220 dogs with primary hypoadrenocorticism and 5 dogs with secondary hypoadrenocorticism (primary ACTH deficiency).
We reviewed medical records of all dogs with naturally occurring hypoadrenocorticism examined at The Animal Medical Center between 1979 and 1993 or at Tufts University, Foster Hospital for Small Animals, between 1987 and 1993.
Dogs ranged from 4 months to 14 years old. Most (71%) were female, and female dogs had a significantly higher relative risk of developing hypoadrenocorticism than did males. Great Danes, Portuguese Water Dogs, Rottweilers, Standard Poodles, West Highland White Terriers, and Wheaton Terriers had a significantly higher relative risk of developing hypoadrenocorticism than did dogs of other breeds. Common owner complaints included lethargy, poor appetite, and vomiting, whereas lethargy, weakness, and dehydration were common abnormalities detected on physical examination. Serum biochemical testing at the time of diagnosis revealed moderate-to-severe azotemia and hyperphosphatemia in most dogs. In 99 of 172 (57.6%) dogs that had a pretreatment urinalysis performed, urine specific gravity was < 1.030 even though dogs were azotemic. Serum electrolyte changes included hyperkalemia (n = 215), hyponatremia (183), hypochloremia (94), and hypercalcemia (69). Five of the 220 dogs with primary hypoadrenocorticism and the 5 dogs with secondary hypoadrenocorticism did not have hyperkalemia at time of diagnosis. In all dogs, ACTH stimulation testing revealed a low to low-normal baseline serum cortisol concentration with little to no rise after ACTH administration. Endogenous plasma ACTH concentration measured in 35 dogs with primary hypoadrenocorticism was markedly high; whereas ACTH concentration was undetectable to low in the 5 dogs with secondary hypoadrenocorticism.
hypoadrenocorticism is a rare disease in dogs, most commonly affecting young to middle-aged females; some breeds are at greater risk of developing the disease than others. In general, clinical signs are nonspecific and similar to manifestations of more common diseases. Serum electrolyte disturbances of hyperkalemia and hypernatremia are characteristic in dogs with primary hypoadrenocorticism, but concentrations may be normal in dogs with early or mild primary or secondary hypoadrenocorticism. Diagnosis of hypoadrenocorticism is best confirmed by demonstration of a low baseline serum cortisol concentration with a subnormal or negligible response to ACTH administration. Determination of endogenous plasma ACTH concentrations is valuable in differentiating primary from secondary hypoadrenocorticism, particularly in dogs with normal serum electrolyte concentrations.
... 6,12 Thyroid autoantibodies were assessed in 6 dogs, with positive finding in 4 cases. 6,8,12,14,15 Moreover, hypothyroidism has been documented in 4% of dogs with hypoadrenocorticism. 16 The study does not classify this occurrence as polyendocrine syndrome, and the authors do not specify whether these dogs exhibited autoantibodies. 16 To our knowledge, there are no extensive studies investigating the prevalence of thyroid autoantibodies in dogs with hypoadrenocorticism during the chronic treatment of the disease. ...
... 6,8,12,14,15 Moreover, hypothyroidism has been documented in 4% of dogs with hypoadrenocorticism. 16 The study does not classify this occurrence as polyendocrine syndrome, and the authors do not specify whether these dogs exhibited autoantibodies. 16 To our knowledge, there are no extensive studies investigating the prevalence of thyroid autoantibodies in dogs with hypoadrenocorticism during the chronic treatment of the disease. Additionally, the evaluation of thyroid function in dogs with primary hypoadrenocorticism has not been undertaken during chronic treatment of hypoadrenocorticism. ...
... Hypothyroidism was diagnosed concurrently with hypoadrenocorti- was challenging to ascertain which endocrine disorder appeared first or determine the time gap between the 2 diagnoses. 16 The failure of the thyroid gland in hypothyroidism is assumed to be a slowly progressive process in which clinical signs and hormonal changes develop over several years. 24 If initially present, autoantibodies are expected to diminish in the late phase of the disease. ...
Background
Knowledge about primary hypoadrenocorticism coexisting with immune‐mediated thyroiditis (Schmidt's syndrome) in dogs is limited.
Objective
To evaluate thyroid function in dogs with naturally occurring hypoadrenocorticism before and during treatment.
Animals
Sixty‐six client‐owned dogs.
Methods
Measurement of canine thyroid stimulating hormone (cTSH), total thyroxine (T4), free thyroxine, and autoantibodies against thyroglobulin, T4, and total triiodothyronine.
Results
Thirty‐eight dogs were assessed before and 28 during treatment. Follow‐up data were available for 24/38 and 17/28 dogs, with median follow‐up duration of 3.8 years (range, <1.0‐8.8 years) and 4 years (range, 1.1 weeks to 10.5 years), respectively. Canine thyroid stimulating hormone was above the reference range at the time of diagnosis of hypoadrenocorticism in 10 of 38 dogs but decreased into the reference range in 7 for which follow‐up data was available. Hypothyroidism was confirmed in 5 dogs at a median age of 11 years (range, 7‐15 years). In 4 dogs, the condition was diagnosed after a median treatment duration of 5.75 years (range, 2.6‐10 years), while in 1 dog, the diagnosis was made concurrently. One dog had detectable thyroid autoantibodies.
Conclusions and Clinical Relevance
Hypothyroidism occurs as a rare concurrent condition in dogs with hypoadrenocorticism, potentially at any phase of treatment. Close monitoring of cTSH levels in these dogs could be beneficial, as early changes might indicate the onset of hypothyroidism. The low prevalence of detectable thyroid autoantibodies suggests that nonimmune mechanisms might contribute to thyroid dysfunction.
... However, it is an important disease because of its potential for significant morbidity and mortality and tendency towards a higher prevalence in certain breeds. Primary hypoadrenocorticism is considered to account for the majority (> 90%) of cases [28] and is presumed to result from autoimmune destruction as supported by the presence of circulating autoantibodies against cytochrome P450 sidechain cleavage enzyme and histopathological evidence of lymphocytic adrenalitis in some affected dogs [4,9,10]. Nevertheless, other pathologies that result in adrenal destruction, including neoplasia, tuberculosis, granulomatous diseases and haemorrhage can occur, albeit rarely [15,23]. ...
... Since the first large case series describing hypoadrenocorticism in dogs was published, it has been known that not just dogs with secondary disease but also some with primary disease present with evidence of glucocorticoid deficiency alone [28]. These are often called atypical cases or more recently, as suggested by the European Society of Veterinary Endocrinology, eukalaemic, eunatraemic hypoadrenocorticism (EEH) stratified by being primary or secondary, if evaluated. ...
... Selective destruction of the zonae fasciculata and reticularis with relative sparing of the zona glomerulosa has been described [1,22]. Symptomatic therapy, particularly intravenous fluids, could potentially mask pre-existing electrolyte abnormalities [28]. Additionally, dogs with known mineralocorticoid deficiency can maintain electrolyte concentrations within reference interval through unknown mechanisms [2]. ...
Background
Naturally occurring hypoadrenocorticism is an uncommon endocrine disorder in dogs but has significant morbidity and mortality. Some dogs present with apparent glucocorticoid deficiency alone as evidenced by eunatraemia and eukalaemia. Few studies have compared dogs with hypoadrenocorticism with or without electrolyte disturbances and there are no large case series of affected dogs from Ireland.
Methods
Retrospective observational study.
Results
Ninety-two cases diagnosed with hypoadrenocorticism subdivided into those with supportive electrolyte disturbances (Group 1; n = 72) and those without (Group 2; n = 20). Dogs in Group 1 were significantly ( p = 0.001) younger (4.0 (3.0–6.0) years) than dogs in Group 2 (6.0 (4.75–8.25) years). Dogs in Group 1 presented significantly more commonly with vomiting (Group 1: 52/71 (73.2%), Group 2: 6/20 (30.0%); p < 0.001), total hyperproteinaemia (Group 1: 21/71 (29.6%), Group 2: 1/20 (5.0%); p = 0.023), increased urea (Group 1: 52/72 (72.2%), Group 2: 5/20 (25.0%); p < 0.001), increased creatinine (Group 1: 31/72 (43.1%), Group 2: 3/20 (15.0%); p = 0.021) and hyperphosphataemia (Group 1: 40/71 (56.3%), Group 2: 2/20 (10.0%); p < 0.001), and significantly less commonly with reticulocytosis (Group 1: 4/38 (10.5%), Group 2: 5/13 (38.5%), p = 0.023). An undetectable basal aldosterone concentration had a positive predictive value of 94.3% for diagnosing undetectable post-ACTH aldosterone concentration. Of the thirteen dogs in Group 2 that had aldosterone concentrations measured and secondary disease excluded, 7 (53.8%) had or subsequently developed evidence of aldosterone deficiency, although not always with electrolyte abnormalities.
Conclusions
Dogs with hypoadrenocorticism from Ireland are similar to other reported cases. An undetectable basal aldosterone concentration is highly predictive of mineralocorticoid deficiency. Dogs with apparent glucocorticoid deficiency alone can progress to more typical disease and should be monitored appropriately.
... A forma primária causada pela destruição imunomediada do córtex das glândulas adrenais, é mais comum em cães (Guzmán Ramos et al., 2022). O HA é uma doença que está associada à uma gama de alterações clínicas e laboratoriais, que podem ser severas ou leves, consistentes ou variáveis, agudas ou crônicas (Spence et al., 2018) e similares a alterações vistas em uma variedade de doenças mais comuns (Kintzer & Peterson, 1997;Peterson et al., 1986Peterson et al., , 1996. ...
... A apresentação dos sinais clínicos do HA pode variar de acordo com o "estágio" da doença (Lathan & Thompson, 2018;Scott-Moncrieff, 2015;Van Lanen & Sande, 2014;Wakayama et al., 2017). A maioria dos cães já apresentam um histórico de alterações crônicas no momento do diagnóstico e os sinais clínicos normalmente não mudam com o passar do tempo, porém pioram de forma marcante fazendo com que o paciente entre em crise aguda da doença, chamada de crise addisoniana (Kintzer & PUBVET v.18, n.03, e1558, p.1-11, 2024 Peterson, 1997;Peterson et al., 1986Peterson et al., , 1996. Alterações que devem gerar suspeitas de HA incluem, sinais gastrointestinais crônicos, como êmese intermitente, diarreia e anorexia (Guzmán Ramos et al., 2022), estes que respondem rapidamente a fluidoterapia ou tratamento com corticoides (Scott-Moncrieff, 2015;Van Lanen & Sande, 2014); porém normalmente recidivam em dias ou semanas (Fenner et al., 2020;Paradello, 2023;Paula et al., 2022;Teles et al., 2016). ...
... Após o lançamento, foi sugerida a troca para o tutor, a fim de evitar novas crises addisonianas, levando em consideração que paciente apresentava as dosagens de sódio no limite inferior nos exames, além de apresentar quadros eméticos em situações de estresse sendo necessária a associação de prednisolona ao tratamento. De acordo com a literatura, não há diferença significativa no tempo de sobrevida de pacientes tratados com acetato de fludrocortisona quando comparado com pacientes tratados com DOCP (Kintzer & Peterson, 1997;Peterson et al., 1996;Van Lanen & Sande, 2014). ...
Hipoadrenocorticismo (HA) ou doença de Addison é uma endocrinopatia incomum em cães, com ocorrência principalmente entre um e seis anos de idade. Pode ser classificado de acordo com sua origem, como primário, secundário ou terciário, sendo a forma primária a mais comum, causada pela destruição idiopática imunomediada do córtex da adrenal, que pode resultar na deficiência de mineralocorticoides e/ou glicocorticoides. As manifestações clínicas são inespecíficas. Desta forma, o paciente pode apresentar desde apenas quadros de gastroenterites intermitentes, até hipotensão, tremores, letargia, anorexia e perda de peso. O diagnóstico é realizado na anamnese, sinais clínicos, exames hematológicos, urinálise e ultrassonografia abdominal. No entanto, para o diagnóstico definitivo deve ser feito o teste de estimulação com ACTH (hormônio adrenocorticotrófico), no qual os cães com HA apresentarão resultados abaixo da referência. O tratamento deve ser realizado com base no estado geral do paciente e com a suplementação hormonal, que deve ser avaliada de acordo com a necessidade de cada cão. O presente estudo tem como objetivo relatar o caso de uma cadela da raça Whippet de um ano de idade que foi admitida no serviço de pronto atendimento de um hospital veterinário 24 horas devido a quadro de êmese e anorexia, que evoluíram para uma crise addisoniana. Após o diagnóstico de HA e iniciado o tratamento com prednisolona e acetato de fludrocortisona, a paciente foi acompanhada por 965 dias. Nesse período, apresentou quadros de êmese em situações de estresse, além de apresentar sódio no limite inferior nos exames hematológicos realizados.
... 3 the disease is concentrated in certain breeds. [4][5][6][7][8][9][10] Standard Poodles (STPDs) and Portuguese water dogs (POWDs) have among the highest prevalence, with some studies estimating 8% to 10% being affected. 6,7 Breed predisposition suggests a hereditary component, and genetic contributions have been studied. ...
... 41 These data were joined to participant data by location of the county; participants were assigned the overdose death rate for their county of residence. All spatial joins were performed in ArcGIS version 10 ...
Background
Primary hypoadrenocorticism in dogs is thought to be multifactorial with roles for both genetic and environmental factors. The contributions of environmental factors remain unexplored.
Objective
Identify environmental and lifestyle exposures associated with primary hypoadrenocorticism in 2 dog breeds with high risk of developing the disease.
Animals
Animals were not used in this study. Owners of Standard Poodles (STPDs) and Portuguese water dogs (POWDs) participated in a survey.
Methods
Retrospective case‐control study. Dog owners were invited to participate in an online survey through convenience sampling. Questions regarded the demographics, health histories, and indoor/outdoor environments in which their dogs live and play. Responses for dogs with primary hypoadrenocorticism were compared to those without the disease using univariate and multivariate logistic regression models.
Results
Five thousand forty‐seven responses (358 cases, 4689 controls) met initial inclusion criteria. Significant associations with modest effect size were found for community type, ingestion of canned food, and use of lawn fertilizer in some analysis models. Reproductive (spay/neuter) status exhibited the strongest association with high effect size across all models with adjusted odds ratio (OR) 2.5 (95% confidence interval [CI], 1.4‐4.5; P = .003) for spayed females and 6.0 (95% CI, 2.6‐13.9; P < .001) for neutered males.
Conclusions and Clinical Importance
The large effect size for reproductive status reflects its high potential clinical relevance, whereas modest effect sizes for other environmental variables suggest lower potential clinical relevance. These findings are associations and do not necessarily imply causation. Before any actionable recommendations are warranted, additional evidence regarding biological mechanisms is needed.
... Hypoadrenocorticism (HA) is an uncommon disease in dogs. 1 Dogs with HA frequently are presented with chronic nonspecific clinical signs, including anorexia, vomiting, weight loss, and diarrhea. [2][3][4][5] Because of the vague clinical signs, dogs with HA and, in particular, those with eunatremic, eukalemic HA (EEH), often receive empirical treatment with glucocorticoids (GCs) before reaching a final diagnosis. ...
Background
In dogs, duration of hypothalamic‐pituitary‐adrenal (HPA) axis suppression after systemic glucocorticoid treatment is reported to vary from a few days to up to 7 weeks after glucocorticoid discontinuation. These data are derived mainly from experimental studies in healthy dogs and not from animals with spontaneous disease.
Hypothesis and Objective
To determine the timeline for recovery of the HPA axis in a group of ill dogs treated with intermediate‐acting glucocorticoids (IAGCs).
Animals
Twenty client‐owned dogs that received IAGC for at least 1 week.
Methods
Single‐center prospective observational study. An ACTH stimulation test, endogenous ACTH concentration, serum biochemistry profile, and urinalysis were performed at T0 (2‐6 days after IAGC discontinuation) and then every 2 weeks (eg, T1, T2, T3) until HPA axis recovery was documented (post‐ACTH cortisol concentration > 6 μg/dL).
Results
The median time of HPA axis recovery was 3 days (range, 2‐133 days). Eleven of 20 dogs showed recovery of the HPA axis at T0, 6/20 at T1, and 1 dog each at T2, T5, and T9. Dose and duration of treatment were not correlated with timing of HPA axis recovery. Activities of ALT and ALP were significantly correlated with the post‐ACTH cortisol concentration (rs = −0.34, P = .03; rs = −0.31, P = .05). Endogenous ACTH concentration was significantly correlated with pre (r = 0.72; P < .0001) and post‐ACTH cortisol concentrations (r = 0.35; P = .02). The timing of HPA axis recovery of the dogs undergoing an alternate‐day tapering dose was not different compared to dogs that did not (3.5 vs 3 days, P = .89).
Conclusion and Clinical Importance
Most dogs experienced HPA axis recovery within a few days after IAGC discontinuation. However, 2/20 dogs required >8 weeks.
An 8‐year‐old, female, spayed Kelpie cross presented with hyporexia, pica, vomiting, collapse and seizures. It was diagnosed with eunatraemic, eukalaemic hypoadrenocorticism, immune‐mediated anaemia and immune‐mediated thrombocytopenia, possibly representing an example of multiple autoimmune syndrome type 3. All abnormalities resolved and the patient was alive nearly 3 years later, maintained on physiological doses of prednisolone. This case serves as a reminder of the variable presentations of eunatraemic, eukalaemic hypoadrenocorticism and the potential for concurrent immune‐mediated disease.
Zusammenfassung
Das autoimmune polyendokrine Syndrom (APS) ist eine beim Hund selten vorkommende Kombination autoimmun bedingter endokriner Erkrankungen. Häufige Kombinationen sind Hypothyreose mit Hypoadrenokortizismus oder Diabetes mellitus. Des Weiteren können seltener Hypoparathyreoidismus und Orchitis als Teil eines APS auftreten. Die Diagnose des APS erfolgt über die Diagnose der jeweiligen Erkrankungen. Ebenso besteht die Therapie des APS in der Therapie der beteiligten Erkrankungen, d.h. in der Substitution der defizienten Hormone. Entstehen unter einer zuvor stabilen Therapie einer endokrinen Erkrankung weitere Symptome (z.B. Polyurie, Polydipsie oder Gewichtsverlust), sollte an die zusätzliche Entstehung anderer Endokrinopathien wie Hypoadrenokortizismus oder Diabetes mellitus gedacht werden. Die Diagnose der initial diagnostizierten Endokrinopathie sollte jedoch ebenfalls kritisch hinterfragt werden. Dieser Artikel fasst Fallberichte aus dem eigenen Patientengut sowie ausgewählte Fallberichte aus der Literatur mit ihren Besonderheiten zusammen.
We evaluated the effect of ovine corticotropin-releasing hormone (CRH) on plasma immunoreactive (IR) concentrations of ACTH, alpha-melanocyte-stimulating hormone, and cortisol in 8 dogs with naturally acquired adrenocortical insufficiency. Of the 7 dogs with primary adrenal insufficiency, 6 had markedly high basal plasma IR-ACTH concentrations and exaggerated ACTH responses to CRH administration, whereas 1 dog that was receiving replacement doses of prednisone at the time of testing had normal basal IR-ACTH concentrations and a nearly normal response to CRH. In contrast, the 1 dog with secondary adrenocortical insufficiency had undetectable basal plasma IR-ACTH concentrations, which failed to increase after administration of CRH. Basal plasma alpha-melanocyte-stimulating hormone concentrations in the dogs with adrenal insufficiency were within normal range and were unaffected by CRH administration. In all 8 dogs with adrenal insufficiency, plasma cortisol concentrations were low and did not increase after administration of CRH. Therefore, stimulation with CRH produced 2 patterns of plasma IR-ACTH response when administered to dogs with naturally acquired adrenal insufficiency. Dogs with primary adrenal insufficiency had high basal plasma IR-ACTH concentrations and exaggerated responses to CRH, whereas the dog with secondary adrenal insufficiency had undetectable basal plasma concentrations of IR-ACTH that did not increase after stimulation with CRH.
Isolated ACTH deficiency is a rare disorder. We report four cases of this disease which presented to the Department of Endocrinology at Leeds General Infirmary over a one‐year period. The diagnostic clinical and biochemical features of each case are discussed and the pertinent literature is reviewed. The clinical investigations vary somewhat between cases as the four patients presented in markedly different ways. Well validated dynamic endocrine investigations were employed including glucagon stimulation test (GST) and the corticotrophin releasing hormone (CRH) test (using 100 μg of human CRH with samples for ACTH and cortisol). Two patients probably had CRH deficiency and two had ACTH deficiency. All the cases are instructive, illustrating different features of this heterogeneous condition.
We conclude that the diagnosis of this condition may be difficult due to the varied clinical presentation. We suggest that it is commoner than previously thought and that the precision of diagnosis can be improved using the CRH test.
The efficacy of a microcrystalline desoxycorticosterone pivalate (DOCP) injection in the management of canine hypoadrenocorticism (CHAC) was investigated in 21 dogs. On day 0 dogs previously diagnosed with CHAC were given a physical examination and an injection (2.2 mg/kg) of DOCP. This was repeated on days 25 and 50. On day 75 of the study a final physical examination was performed and the success of therapy was evaluated. Blood samples were obtained for serum chemical analysis (Na+, K+, Cl-, BUN & creatinine) on day 0 and day 75. Body weight increased steadily from a mean (+/- SD) of 25.5 +/- 14.2 kg on day 0 to 27.1 +/- 14.8 kg on day 75. The mean serum biochemistry values on day 0 were outside normal limits for Na+ (139.3 +/- 9.2 mEq/l), K+ (5.4 +/- 0.9 mEq/l), and Na+/K+ ratio [(26.4 +/- 4.8)/l]. On day 75, after three injections of DOCP, the values for Na+ (148.2 +/- 5.2 mEq/l), K+ (4.9 +/- 0.6 mEq/l), and Na+/K+ [(30.8 +/- 4.2)/l] were normal and significantly (P less than 0.01) different from values on day 0. All dogs in the study did well on DOCP therapy. The few side effects observed resolved with concomitant administration of prednisolone and/or adjustment of the DOCP dose. All clients elected to continue DOCP therapy after the trial ended, and the dogs continue to do well.
The efficacy of microcrystalline desoxycorticosterone pivalate (DOCP) therapy was evaluated in 60 dogs with hypoadrenocorticism. Fifty-one of the dogs were being treated with either DOCP or fludrocortisone acetate prior to entering the study. The disease had been recently diagnosed in 9 dogs that were not under maintenance treatment prior to entering the study. Desoxycorticosterone pivalate (2.2 mg/kg of body weight, IM) was administered on days 0, 25, and 50. Physical examination was performed, and blood samples were obtained for serum biochemical analysis (Na+, K+, and BUN concentrations) on days 0, 14, 25, 39, 50, 64, and 75. On day 75 of the study, a final physical examination was performed and the course of treatment was evaluated. Sixty-eight percent (41/60) of the dogs had normal physical findings on day 0 vs 87% (52/60) on day 75. Mean (+/- SD) body weight increased from 24.8 +/- 12.7 kg on day 0 to 26.2 +/- 13.7 kg on day 75. Mean serum Na+ (137.7 +/- 8.5 mEq/L) and K+ (5.6 1.0 mEq/L) concentrations and Na(+)-to-K+ ratio (25.4 +/- 5.0:1) were outside normal reference limits on day 0. By day 75, serum Na+ (144.3 +/- 4.8 mEq/L) and K+ (4.9 +/- 0.8 mEq/L) concentrations and Na(+)-to-K+ ratio (30.4 +/- 5.1:1) were normal and were significantly (P < 0.01) improved, compared with the corresponding values on day 0. Of the 60 dogs, 58 (97%) regained the loss in body weight, appetite, and muscular strength while given DOCP; once achieved, these improvements were maintained. These 58 dogs did not vomit or have diarrhea, common problems in dogs with hypoadrenocorticism.(ABSTRACT TRUNCATED AT 250 WORDS)