There is more to hypothyroidism than alopecia...(Proceedings)

The hypothyroid patient can present with countless symptoms, all related to the underlying cause. As is the case with allergic dermatitis, these patients are typically pruritic, however the pruritus in these situations is due to secondary bacterial and yeast infections, not an allergic disorder. Because thyroid hormone is essential for hair growth, for the process of keratinization to occur normally and for sebaceous glands to function properly, patients with hypothyroidism frequently present with secondary infections directly related to these abnormalities of the skin and hair coat. Seborrheic changes occur from altered keratinization and altered fatty acid concentrations, which can also occur in many patients with allergic dermatitis, thus one reason for the confusion. Overlap can occur between endocrine disorders and the three main allergic syndromes and it is not uncommon to come across a patient that suffers from an allergic disorder that has been repeatedly tested for hypothyroidism or vice versa. Why? Does this make sense? How can we differentiate between those dogs with endocrine disease and those with allergic disease?

Hypothyroidism in the dog

Multiple etiologies for hypothyroidism in the dog exist, the most common of which is primary hypothyroidism. Primary hypothyroidism is synonymous with a problem of the gland itself, usually through destruction. Lymphocytic thyroiditis and idiopathic atrophy both result in progressive damage to the gland and the resulting lack of production of relevant hormones.

**Primary hypothyroidism = ↓T4 and ↑TSH with lack of response to TSH and/or TRH testing, if performed.**

Secondary hypothyroidism is synonymous with a problem of the pituitary gland and impaired secretion of thyroid stimulating hormone, resulting in lack of secretion of thyroid hormones and thyroid gland atrophy, but without initial damage to the thyroid gland. The most common cause for secondary hypothyroidism is suppression of pituitary thyrotroph cells via drugs or hormones, however pituitary neoplasia and pituitary hypoplasia, resulting in disproportionate dwarfism, can also occur.

**Secondary hypothyroidism = ↓T4 and ↓to undetectable TSH with some response to TSH or TRH testing, if performed.**

Tertiary hypothyroidism has not been reported in the dog. Causes for this disorder in humans include congenital defects, hypothalamic destruction and cellular defects.

Hypothyroidism in the cat

Naturally acquired disease in the cat is quite rare; iatrogenic disease as a consequence of treatment for hyperthyroidism can certainly occur. Cats that have been reported with naturally acquired hypothyroidism typically suffer from congenital disease and disproportionate dwarfism.

Disorders recognized as secondary and tertiary hypothyroidism in the cat have not been reported. Most cats with symmetrical truncal alopecia are in fact pruritic and pulling or barbering their hair, which is most consistent with a parasitic or allergic condition rather than an endocrine disorder.

Diagnosing hypothyroidism: Who?

First and foremost, before testing suspect hypothyroidism. Not every patient with skin disease needs to be tested, or even screened. Always treat and resolve ALL secondary infections before continuing with additional testing. If the patient continues to be pruritic despite complete resolution of all secondary infections, then it is very unlikely the culprit is hypothyroidism. If the patient is NOT pruritic between episodes of secondary infections, then thyroid testing is warranted as indicated below.

The initial workup

In addition, the presence of a dry, dull hair coat along the dorsum may represent retained telogen hairs that are not being replaced by growing, anagen hairs. This dull, dry hair coat may progress into multifocal areas of alopecia, especially in areas of friction, or wear, consistent with a "wear alopecia". Areas over pressure points can develop into focal areas of deep pyoderma, with or without elbow callus pyoderma. Alopecia along the bridge of the nose can also be an early warning sign of hypothyroidism along with recurrent unilateral otitis externa.

Other clinical abnormalities include fasting hypercholesterolemia > 400 mg/dl, fasting hypertriglyceridemia (~70% of patients), normocytic, normochromic, nonregenerative anemia (~30% of patients), elevated liver enzymes as a result of fatty infiltration of the liver, and neurological signs.

Diagnosing hypothyroidism: How?

The diagnostic test options available today can make the definitive diagnosis of canine hypothyroidism quite challenging. Because of the low sensitivity and specificity of most commercially available test modalities as well as potential interference from drugs, hormones and systemic illness it is crucial to consider patient selection as well as confounding drug therapy when performing thyroid testing. Focus on clinical history, physical examination findings and screening lab work before going on to thyroid testing.

Factors resulting in decreased Total T4 concentrations:

1. Hypoproteinemia: Thyroxine (T4) is highly protein bound, thus if less protein is available for binding, less will be bound resulting in a lower Total T4 value.

2. Concurrent illness: Impaired binding of thyroxine to plasma carrier proteins.

3. Drug therapy:

     • Glucocorticoids = ↓T4 , T3 in 1 - 3 days; variable TSH concentrations.

     • Sulfonamides = ↓T4 , T3; ↑TSH within 21 days.

     • Phenobarbital = ↓T4 , T3 due to increased metabolism; delayed ↑TSH

Negative feedback loops:

THE thyroid panel:

What about in-house testing?

Controversy still exists regarding the use of in-house ELISA test kits for measurement of Total T4. Results from a few studies evaluating the methodology have not been in agreement. Caution is advised when using in-house testing and consideration for the physical exam findings as well as clinical suspicion for the disease should be taken into account when performing thyroid testing in suspect patients.

Diagnosing hypothyroidism: Which tests are valuable to the clinician?

Therapeutic trials:

Often times test results in a suspect patient do not result in a clear-cut diagnosis. In these situations a therapeutic trial should be considered. It is important to remember that whichever clinical sign present that prompted the initial investigation should improve significantly with appropriate supplementation. Because it is impossible to predict which patients will respond to once daily versus twice daily supplementation, the initial trial is performed with twice daily dosing. Post-pill total T4 measurement is performed 4 - 6 weeks following institution of therapy. With twice-daily administration a 4 - 6 hours post-pill total T4 is typically evaluated; results should be in the high-normal range. Some clinicians prefer to obtain a sample just before the next dose is to be administered.