CONDITION
Atypical Cushings in Dogs
Atypical Cushing's disease describes a pattern in which a dog shows signs often associated with Cushing's syndrome—such as hair loss, increased thirst and urination, or a pot-bellied appearance—but standard tests for cortisol excess come back normal. In these cases, the adrenal glands may be overproducing other steroid hormones, particularly sex-hormone intermediates such as 17-hydroxyprogesterone, androstenedione, progesterone, or oestradiol, rather than cortisol itself. The clinical picture can look identical to classic Cushing's, which is why owners and clinicians may pursue further investigation when initial screening does not explain what is being observed. This is an uncommon and somewhat debated variant; not all specialists agree on whether the elevated sex-hormone intermediates are directly responsible for the signs, or whether subtle cortisol abnormalities still play a role. The condition tends to affect middle-aged to older dogs, and the underlying cause may be adrenal hyperplasia, an adrenal tumour, or a pituitary abnormality driving excess hormone production. Diagnosis relies on measuring a broader panel of adrenal steroid hormones, typically after stimulation with ACTH, to reveal the pattern of excess that standard tests miss. This page explores what an owner may observe, the mechanisms that may be at work beneath the surface, how the condition is investigated using extended hormone panels, and the medical and sometimes surgical approaches that exist. The aim is to provide context for conversations with your clinical team and to help you understand what may be happening when a familiar set of signs does not fit the usual diagnostic pathway.
Why this matters now
Atypical Cushing's tends to be recognised in middle-aged to older dogs, typically between eight and twelve years of age, though cases have been documented in animals as young as three. Scottish Terriers show a well-documented breed predisposition to this pattern of adrenal sex-hormone excess, linked to a genetic locus near HSD17B2, though the condition can also occur in other pedigree and mixed-breed dogs without a known familial link. Recognition often follows investigation of signs that resemble classical Cushing's syndrome, but where standard cortisol testing has returned normal results.
The progression of atypical Cushing's can be gradual and variable between individuals. Some dogs may remain stable with mild signs for extended periods, while others develop more pronounced changes in coat quality, body shape, or thirst patterns over months to years. There is ongoing discussion within veterinary endocrinology about whether atypical Cushing's may represent an early stage of classical disease in some animals, or whether it constitutes a distinct and separate hormonal pattern. The trajectory in any given dog remains difficult to predict at the outset.
Signals & patterns
Early signals
Increased drinking and urination
An owner may notice the water bowl being emptied more frequently, or requests to go outside becoming more persistent, particularly overnight. The volume of urine passed may also increase, and accidents indoors can occur in previously reliable dogs.
Subtle coat changes
The coat may begin to lose its usual texture or sheen, appearing duller or slightly brittle. Hair regrowth after clipping can slow, and areas of thinning may emerge gradually, often symmetrically on the flanks or trunk.
Changes in appetite or weight distribution
Some dogs develop a more persistent interest in food, whilst others may show a gradual redistribution of body fat towards the abdomen, even without substantial weight gain. The belly may appear more rounded or pendulous over time.
Reduced activity or stamina
An owner may observe that their dog tires more easily on familiar walks, or prefers to rest rather than engage in activities they previously enjoyed. The change can be subtle and may initially be attributed to normal ageing.
Later signals
Progressive hair loss
More extensive symmetrical thinning or baldness can develop across the trunk, flanks, and tail, often sparing the head and legs. The skin in these areas may become darker or develop a mottled appearance, and the remaining coat may feel thin or woolly.
Skin fragility or recurrent infections
The skin may become noticeably thinner, bruising more easily or tearing with minor trauma. Some dogs develop recurrent skin infections, blackheads (comedones), or secondary parasitic infestations such as demodicosis that had not previously been problematic.
Muscle weakness or wasting
Muscle mass, particularly over the limbs and shoulders, may diminish, giving a more bony appearance. Some dogs develop a pot-bellied stance or difficulty rising from rest, and in advanced cases weakness can affect mobility or posture.
Click to read about the biological mechanisms
How this is usually investigated
Investigation typically begins with a detailed history and physical examination, followed by initial screening tests to assess general metabolic function and rule out other causes of similar signs. When initial findings are consistent with adrenal disease but standard cortisol tests are normal or inconclusive, more specialised hormone measurements may be considered. The diagnostic process often unfolds in layers, with each step helping to clarify whether atypical patterns are present.
Chemistry panel
ACTH stimulation test
Adrenal hormone panel (sex steroid precursors)
Abdominal ultrasound
Histopathology
Options & trade-offs
Management is typically tailored to the individual dog, taking into account the severity of signs, adrenal imaging findings, and the owner's practical circumstances. Some owners and clinicians elect to monitor without intervention if signs are mild or stable, while others pursue medical or surgical approaches when signs progress or quality of life is affected. Different combinations of approaches can be workable, and the choice often reflects a balance between what is achievable and what the animal tolerates.
Monitoring without intervention
For dogs with mild or stable signs, periodic reassessment of clinical signs, body weight, coat quality, and routine bloodwork may be chosen, without active hormonal suppression. This approach allows time to observe whether the condition progresses or plateaus. Some dogs remain stable for extended periods, while others show gradual worsening that prompts reconsideration of more active management.
Trade-offs: Monitoring avoids the costs and risks of medication or surgery, but does not alter the underlying hormone production. It may suit dogs with minimal signs or those with concurrent health issues that complicate other approaches, though it requires tolerance of ongoing changes and regular review.
Mitotane (Lysodren) therapy
Mitotane selectively destroys cells in the adrenal cortex that produce both cortisol and sex hormones, leading to a reduction in circulating levels of both hormone classes. Treatment is typically initiated with a loading phase, followed by maintenance dosing, and requires regular monitoring of adrenal function and clinical response. Many dogs show improvement in signs such as coat quality, polyuria, and polydipsia over weeks to months.
Trade-offs: Mitotane can produce hypoadrenocorticism if dosing is excessive, and requires careful titration and owner compliance with monitoring. It may not suit all owners due to the need for frequent follow-up during the induction phase, and some dogs show incomplete or variable response.
Trilostane therapy
Trilostane inhibits 3-beta-hydroxysteroid dehydrogenase, an enzyme in the adrenal steroidogenic pathway. In dogs with atypical Cushing's, this inhibition often paradoxically increases sex hormone precursor concentrations—including 17-hydroxyprogesterone, androstenedione, and oestradiol—rather than reducing them, due to shunting of precursors through unblocked pathways and loss of negative feedback as cortisol falls and ACTH rises. For this reason, many clinicians consider trilostane inappropriate for atypical cases, reserving it for classical Cushing's disease where cortisol suppression is the primary goal.
Trade-offs: The potential for worsening sex hormone levels makes trilostane poorly suited to atypical Cushing's in many cases. It may be considered if there is concurrent cortisol excess, but careful hormone monitoring is needed, and clinical improvement is less predictable than with mitotane.
Surgical adrenalectomy
Removal of one or both adrenal glands can be considered when imaging identifies a unilateral adrenal tumour or when medical management is not effective or tolerated. Unilateral adrenalectomy may resolve signs if the opposite gland remains functional and non-hyperplastic. The procedure requires specialist surgical expertise and carries risks related to anaesthesia, haemorrhage, and proximity to major blood vessels.
Trade-offs: Surgery offers the possibility of definitive resolution if a discrete tumour is present, but is not suitable for all dogs, particularly those with bilateral disease or significant concurrent illness. Post-operative complications can include transient hypoadrenocorticism, and recovery requires careful monitoring.
Common misconceptions
"If standard Cushing's tests are normal, the dog cannot have an adrenal hormone problem."
Standard tests for Cushing's syndrome measure cortisol, not the sex hormone precursors that are elevated in atypical cases. A normal ACTH stimulation test or low-dose dexamethasone suppression test does not exclude atypical adrenal hormone excess, and further specialised testing may be needed if clinical signs suggest adrenal involvement despite normal cortisol results.
"Atypical Cushing's is a less serious or milder version of classical Cushing's disease."
The term 'atypical' refers to the hormonal pattern, not the severity of disease. Some dogs with atypical Cushing's have mild or slowly progressive signs, while others experience significant metabolic effects or quality-of-life impact. The distinction lies in which hormones are elevated, rather than in the degree of illness or the need for management.
"All dogs with elevated sex hormones need treatment."
The degree to which elevated sex hormone precursors produce observable signs or affect well-being varies considerably between individuals. Some dogs with measurable hormone elevations show minimal clinical signs and may be managed with observation alone, while others benefit from active intervention. The decision to treat typically reflects the presence and progression of signs, rather than hormone levels in isolation.
Related conditions
Adrenal Tumours
Adrenal tumours can be the underlying cause of atypical Cushing's disease when the tumour produces sex-hormone intermediates rather than cortisol. The clinical signs may be identical, and diagnosis often relies on imaging to identify the adrenal mass alongside hormone panels that reveal the pattern of excess steroids.
Pituitary Macroadenoma
A pituitary macroadenoma may drive atypical Cushing's disease by sending abnormal signals to the adrenal glands, prompting them to overproduce sex-hormone intermediates instead of cortisol. In some cases, the same pituitary abnormality that causes classic Cushing's can present with this atypical hormone pattern.
Steroid Hepatopathy
Steroid hepatopathy can develop in dogs with atypical Cushing's disease if the overproduction of sex-hormone intermediates has metabolic effects similar to cortisol excess, or if subtle cortisol abnormalities are also present. Liver enzyme elevation and glycogen accumulation in liver cells may be observed in both conditions.
Hypothyroidism in Dogs
Hypothyroidism in dogs can produce overlapping signs with atypical Cushing's disease, including hair loss, lethargy, and weight changes, which may prompt investigation of both endocrine axes. Some dogs may have concurrent thyroid and adrenal dysfunction, and distinguishing between the two often requires careful interpretation of hormone panels.
Sertoli Cell Tumour
Sertoli cell tumours can produce oestrogen and other sex hormones, creating a clinical picture that may resemble atypical Cushing's disease, particularly in intact male dogs with symmetrical hair loss and skin changes. The hormone profiles differ in origin, but both conditions involve abnormal sex-steroid production affecting metabolism and appearance.
If your dog has been investigated for signs consistent with adrenal disease, understanding how atypical patterns differ from classical Cushing's syndrome can be a useful step. The broader context of metabolic health—including how different hormone systems interact and how ageing affects endocrine function—may also offer perspective. For dogs undergoing treatment, periodic reassessment of clinical response and quality of life over time can help inform adjustments to the approach, and this is often a conversation that unfolds across multiple appointments.