Pituitary pars intermedia dysfunction (PPID), formerly known as Equine Cushing's Disease, is the most common endocrine disorder of aged horses. PPID affects approximately 20-25% of horses over 15 years of age.
Overview and Clinical Importance
Pituitary pars intermedia dysfunction (PPID), formerly known as Equine Cushing's Disease, is the most common endocrine disorder of aged horses. PPID affects approximately 20-25% of horses over 15 years of age. Unlike human and canine Cushing's disease (which affects the pars distalis), equine PPID specifically affects the pars intermedia of the pituitary gland. The disease results from oxidative neurodegeneration of dopaminergic neurons in the hypothalamus, leading to loss of inhibitory control over melanotropes in the pars intermedia.
Understanding PPID is critical for NAVLE success as it appears frequently in questions involving geriatric horse care, laminitis workup, and endocrine testing. Early recognition and treatment significantly improves quality of life and survival.
| Peptide |
Function |
Clinical Significance in PPID |
| ACTH |
Stimulates adrenal cortisol production |
Primary diagnostic marker; largely biologically inactive in PPID |
| ?-MSH |
Regulates coat color and hair growth |
Contributes to hypertrichosis; potential diagnostic marker |
| ?-Endorphin |
Endogenous opioid; analgesia and sedation |
Contributes to lethargy; may mask laminitis pain |
| CLIP |
May influence insulin secretion |
May contribute to insulin dysregulation |
Pathophysiology
Normal Pituitary Function
The equine pituitary gland consists of three main regions: the pars distalis (anterior lobe), pars intermedia (intermediate lobe), and pars nervosa (posterior lobe). The pars intermedia contains melanotrope cells that are directly innervated by dopaminergic neurons from the hypothalamus. Dopamine acts on D2 receptors to inhibit melanotrope proliferation and proopiomelanocortin (POMC) transcription.
Pathophysiology of PPID
PPID develops due to oxidative stress-induced neurodegeneration of hypothalamic dopaminergic neurons. This loss of dopaminergic inhibition results in: hyperplasia or adenoma formation in the pars intermedia, overproduction of POMC-derived peptides including ACTH, alpha-melanocyte stimulating hormone (?-MSH), beta-endorphin (?-END), and corticotropin-like intermediate lobe peptide (CLIP).
High-YieldUnlike human and canine Cushing's disease, horses with PPID typically do NOT have elevated plasma cortisol concentrations despite elevated ACTH. The ACTH produced by the hyperplastic pars intermedia is largely biologically inactive. This is why PPID is now the preferred term over 'Equine Cushing's Disease.'
POMC-Derived Peptides and Their Effects
| Clinical Sign |
Prevalence |
Clinical Notes |
| Hypertrichosis |
70% (pathognomonic) |
Long, curly, non-shedding coat; may start with delayed shedding or regional retention (legs, ventrum, throatlatch) |
| Laminitis |
49% |
Often first presenting complaint; associated with concurrent insulin dysregulation; may be masked by ?-endorphin |
| Muscle Wasting |
Common |
Epaxial muscle atrophy (poor topline); Type 2A and 2B fiber atrophy; calpain-mediated proteolysis |
| Pendulous Abdomen |
Common |
Pot-bellied appearance due to muscle wasting and redistribution |
| Lethargy |
4-95% |
Attributed to elevated ?-endorphin; more common in older horses with PPID |
| Polyuria/Polydipsia |
31% |
May result from compression of pars nervosa (reduced ADH); difficult to assess in pastured horses |
| Recurrent Infections |
35% |
Immunosuppression; reduced neutrophil function; increased susceptibility to dermatophilosis, sinusitis, abscesses |
| Hyperhidrosis |
Variable |
Excessive sweating; more common in warm climates; can progress to anhidrosis |
| Abnormal Fat Distribution |
Variable |
Supraorbital fat pads, cresty neck, fat deposits over tailhead |
Signalment and Risk Factors
Age: Primary risk factor. Most horses diagnosed at 15+ years; rare in horses less than 10 years. Youngest reported cases at 7 years of age. Breed: No definitive breed predisposition, although Morgans and ponies may be more commonly affected. Sex: No sex predilection. Prevalence: 20-25% of horses over 15 years of age.
NAVLE TipTesting for PPID is generally NOT recommended in horses less than 10 years old unless hypertrichosis is present. Age is the single most important risk factor for PPID.
| Parameter |
Details |
| Sample Collection |
EDTA (purple top) tube; no fasting required but avoid grain within 12 hours |
| Sample Handling |
Centrifuge, separate plasma, keep at 4°C; analyze within 24 hours or freeze; avoid multiple freeze-thaw cycles |
| Timing |
Can be performed any time of day; no circadian variation noted |
| Sensitivity |
66-76%; higher in autumn months; lower for early/subclinical disease |
| Specificity |
87-95% |
Clinical Signs
Clinical signs of PPID can range from subtle (early disease) to obvious (advanced disease). Recognition of early signs is crucial for timely intervention.
| Season |
Normal Range |
PPID Threshold |
| Non-Autumn (Dec-July) |
Less than 29 pg/mL |
Greater than 35-40 pg/mL suggestive |
| Autumn (Aug-Nov) |
Less than 47-100 pg/mL (varies by lab) |
Greater than 100 pg/mL suggestive |
Diagnosis
Diagnosis is based on a combination of clinical signs, signalment, and laboratory testing. Hypertrichosis in an aged horse is considered pathognomonic and may be sufficient for diagnosis without laboratory confirmation. However, laboratory testing is recommended to confirm early disease and monitor treatment response.
Basal ACTH Test
The basal (resting) ACTH concentration is the most commonly used diagnostic test. It is simple, requires a single blood sample, and is commercially available.
Seasonal Reference Ranges for Basal ACTH
CRITICAL: ACTH concentrations show significant seasonal variation, with a natural peak in autumn (August-November in Northern Hemisphere). Seasonally adjusted reference ranges MUST be used.
High-YieldAutumn is the BEST time to test for PPID because the magnitude of ACTH elevation is greater in affected horses, increasing test sensitivity. However, use appropriate seasonal thresholds to avoid false positives.
TRH Stimulation Test
The thyrotropin-releasing hormone (TRH) stimulation test is recommended for early or equivocal cases where basal ACTH may be normal or borderline. TRH stimulates melanotropes, causing exaggerated ACTH release in horses with PPID.
NAVLE TipThe TRH stimulation test should NOT be performed immediately after an oral sugar test (OST) used for insulin dysregulation testing, as this may affect results. Wait at least 24 hours between tests.
Overnight Dexamethasone Suppression Test (ODST)
The ODST is no longer recommended as a first-line diagnostic test due to lower sensitivity for early disease and the potential risk of inducing laminitis with dexamethasone administration. The test measures cortisol suppression: collect baseline cortisol at 5 PM, administer 40 mcg/kg dexamethasone IM, then collect second cortisol sample 19-20 hours later. Normal horses suppress cortisol to less than 1 mcg/dL; horses with PPID fail to suppress.
Factors Affecting ACTH Interpretation
| Protocol Step |
Details |
| Step 1 |
Collect baseline ACTH sample (EDTA plasma) |
| Step 2 |
Administer 1 mg TRH IV (0.5 mg for horses less than 250 kg/ponies) |
| Step 3 |
Collect second ACTH sample at 10 minutes post-injection |
| Interpretation |
Normal: Post-TRH ACTH less than 110 pg/mL. PPID: Post-TRH ACTH greater than 200 pg/mL |
| Side Effects |
Transient: yawning, muscle fasciculation, coughing, lip-smacking, flehmen response |
PPID vs. Equine Metabolic Syndrome (EMS)
PPID and EMS are distinct but frequently co-existing conditions. Approximately 30% of horses with PPID also have insulin dysregulation. Horses with both conditions are at particularly high risk for laminitis.
| Factor |
Effect on ACTH |
| Season (Autumn) |
INCREASES ACTH in all horses; use seasonal reference ranges |
| Stress/Pain |
INCREASES ACTH; mild pain unlikely to cause false positive, but severe pain/illness may |
| Transportation |
INCREASES ACTH; test at home environment if possible |
| Sample Handling |
Heat degrades ACTH (false low); keep samples cold |
| Breed |
Some 'thrifty' breeds (Shetland, Welsh ponies) may have higher ACTH in autumn |
Treatment
Pergolide Mesylate
Pergolide mesylate (Prascend) is the only FDA-approved treatment for PPID in horses. It is a synthetic ergot-derived dopamine D2 receptor agonist that restores dopaminergic inhibition of the pars intermedia.
Expected Treatment Response
- ACTH normalization: 60-80% of cases
- Hypertrichosis improvement: 30-100% (may take until next shedding season)
- Laminitis improvement: 32-75%
- NOTE: Pergolide does NOT consistently improve insulin dysregulation or reduce laminitis risk in horses with concurrent hyperinsulinemia
Supportive Management
Prognosis
PPID is a progressive, incurable disease, but with appropriate management, most horses can maintain good quality of life for years. Prognosis is worse in horses with concurrent insulin dysregulation and laminitis. Pergolide treatment is associated with improved survival.
| Feature |
PPID |
EMS |
| Typical Age |
Greater than 15 years |
Any age (often 5-15 years) |
| Primary Defect |
Dopaminergic neurodegeneration |
Insulin dysregulation |
| Hypertrichosis |
Pathognomonic |
Not present |
| Regional Adiposity |
May occur |
Characteristic (cresty neck) |
| Diagnostic Test |
Basal ACTH, TRH stimulation |
Oral Sugar Test (OST), basal insulin |
| Treatment |
Pergolide mesylate |
Diet modification, exercise, (levothyroxine, metformin) |
| Parameter |
Details |
| Starting Dose |
2 mcg/kg PO once daily (1 mg tablet for 500 kg horse) |
| Dose Titration |
Increase in 0.5-1 mg increments monthly until clinical and laboratory improvement |
| Maximum Dose |
4-5 mcg/kg PO once daily |
| Time to Effect |
ACTH reduction within hours; clinical improvement in 6-12 weeks |
| Monitoring |
Recheck ACTH and clinical signs in 1-3 months; then every 6-12 months |
| Side Effects |
Inappetence, diarrhea, colic, lethargy (usually transient); reduce dose if occurs |
| Duration |
LIFELONG treatment required; disease is progressive and incurable |
| Competition Status |
PROHIBITED substance under most equestrian federations |
| Area |
Recommendations |
| Coat Care |
Regular body clipping to prevent overheating and skin infections; provide shade |
| Nutrition |
If insulin dysregulation present: restrict non-structural carbohydrates (NSC less than 10-12%); avoid lush pasture; use grazing muzzle or dry lot; monitor BCS |
| Dental Care |
Regular dental examinations; aged horses prone to dental disease |
| Hoof Care |
Regular farriery; aggressive laminitis prevention and management |
| Parasite Control |
Regular fecal egg counts; PPID horses may have higher parasite burdens due to immunosuppression |
| Infection Prevention |
Prompt treatment of wounds and infections; vaccination per standard protocols; monitor for dermatophilosis |