SYSTEMIC CONDITIONS
Deciphering the Thyroid Riddle
 A basic primer on the etiology and treatment  of various thyroid diseases.
by Deepak Gupta, O.D., .F.A.A.O. and Sonia Gupta, Rp.H., M.S.

Patients who have thyroid disease often present with a wide range of vague and varying symptoms, which often complicate proper diagnosis and management. However, ocular manifestations of thyroid disease are often key indicators for its prognosis. Thus, as primary care optometrists, we need to understand the basics of the variations of thyroid disease and the therapeutic agents used to manage it.

Taking a scientific look

The thyroid gland is a bi-lobed, highly vascularized organ in the anterior region of the neck. It lies slightly inferior to the thalamus and just superior to the pituitary gland. The thyroid gland secretes two significant hormones:

1. Triidothyronine (T3)

2. Thyroxine (T4)

Both of these hormones are highly important in the body's metabolism. T3 is the biologically active form of thyroid hormone because of its ability to bypass the liver. T3 and T4 molecules cause increased basal metabolism, increased oxygen consumption within the mitochondria and increased alertness (secondary to its stimulation of the sympathetic nervous system).

In addition, these hormones cause an increase in heart rate and force of contraction, as well as increases in respiration, the production of blood cells and blood glucose levels. A delicate balance among several organ systems (most notably the pituitary and hypothalamus) mediates the production of these hormones. External factors such as changes in temperature, emotional reactions, anxiety and stress can influence this balance.

Review the variations

Here's a run-down of the diseases the thyroid can cause, as well as management protocols.

Hypothyroidism. A relatively common condition, hypothyroidism falls into three variants:

1. Primary hypothyroidism. This is the most common variant and is an intrinsic defect in the structure or function of the thyroid. Primary hypothyroidism occurs in roughly one in 4,000 to 6,000 births across all races and ethnic backgrounds.

2. Secondary hypothyroidism (a relative lack of thyroid-stimulating hormone (TSH), usually from a malfunction of the pituitary gland, causes this)

3. Tertiary hypothyroidism (decreased levels of TSH caused by insufficient secretion of thyroid-releasing hormone from the hypothalamus).

As with virtually all thyroid disease, hypothyroidism is more common in women. In terms of primary hypothyroidism, the most common type is the atrophic autoimmune variant. Experts link the etiology of this type to late-stage Hashimoto's thyroiditis, which is an autoimmune thyroid disorder that's also referred to as autoimmune thyroiditis. Other common causes of hypothyroidism include destruction of the gland by infection, virus or other processes, such as ablation via irradiation, radioiodine therapy and subtotal or near-total thyroidectomy.

Typical signs and symptoms of hypothyroidism include weight gain, fatigue, intolerance to cold, hoarseness, neck swelling, shortness of breath, angina, depression, dry skin and constipation. Manifestations linked with severe and potentially fatal thyroid deficiency are known as myxedema. These typically include swelling of the hands, feet, face and periorbital tissue.

Laboratory testing often confirms the diagnosis of hypothyroidism (by demonstrating decreased levels of plasma thyroxine [T4], decreased levels of thyroid hormone binding ratio [THBR] or elevated serum levels of TSH [the body's attempt to compensate]).

The general management protocol for hypothyroidism consists of daily T4 replacement in an attempt to bring TSH levels within a normal range. In most patients who start on therapy, check the serum levels every three to four weeks and adjust dosing until you achieve a proper homeostasis with TSH levels. Care and experience are necessary, as thyrotoxicosis (excess thyroid hormone) may result when doses of thyroid hormone exceed 100µg. In such cases, myocardial infarction or arrhythmias can arise as a consequence of drug therapy. Other management options include desiccated thyroid or purified thyroglobulin and triidothyronine.

Nontoxic goiter. Also referred to as enlargement of the thyroid gland, this is the most common endocrine disease. Experts define it as thyroid enlargement that's neither associated with thyrotoxicosis nor caused by a thyroid neoplasm. It's commonly found in poor countries, where it results from insufficient intake of dietary iodine. Practitioners can easily manage early cases with iodine supplements.

Thyroiditis. This condition involves inflammation of the thyroid from unknown causes. It may result in localized stiffness of the neck, ear pain, constitutional complaints and abnormalities of thyroid hormone production. Variations of this condition include subacute thyroiditis or deQuervain's Thyroiditis, which results from a viral infection of the thyroid gland. In many patients, an upper respiratory tract infection precedes this viral infection.

The cardinal symptom of this condition is pain, which patients may say is in the throat (sore throat), ear or lateral neck. Other symptoms include a low-grade fever, increased sweating and generalized fatigue and malaise. From a clinical standpoint, the thyroid gland is often enlarged, firm and tender on palpitation. The inflamed gland releases pre-formed hormone, which induces a transient hyperthyroidism (thyrotoxicosis).

In the vast majority of cases, this disease is self-limiting and resolves spontaneously within several months of initial onset. Confirm diagnosis of subacute thyroiditis by detecting abnormal thyroid hormone concentrations, elevated Westergren erythrocyte sedimentation rate (ESR) and significantly decreased thyroidal radioactive uptake. Management strategies are generally supportive and aimed at patient comfort; they include aspirin, NSAIDs and in rare cases, systemic steroids.

Hashimoto's thyroiditis is a cell-mediated inflammation that commonly presents with a medium-sized goiter, lymphocytic infiltration, autoantibodies and hypothyroidism. As with many other thyroid conditions, it's much more prevalent in women, and it's most frequently seen in patients between the ages 30 and 50 years. Management strategies aim at hormone replacement to stabilize normal thyroid functions and to decrease the size of the goiter. Physicians usually reserve surgical removal of the gland for severe cases only.

Hyperthyroidism. This condition occurs when the thyroid produces too much hormone. A myriad of factors, such as an immunologic reaction (Graves'), inflammation of the gland (thyroiditis), toxic thyroid nodules (abnormal tissue growth), pituitary tumor (tumor produces excess TSH) and pituitary resistance (disruption of the feedback loop leading to excess TSH release), can cause this condition. Typical patient symptoms of the resulting thyrotoxicosis include nervousness, anxiety, weight loss, restlessness, cardiac arrhythmia and fatigue.

Two major types of hyperthyroidism exist:

1. Graves' disease, which involves the entire thyroid and ultimately destroys the gland.

2. Toxic Nodular disease. Most of the thyroid gland itself remains normal, except the nodule has escaped from normal control and produces excess thyroid hormone.

The management strategy for patients suffering from hyperthyroidism usually begins with a drug regimen (usually oral radioactive iodine swallowed in a water solution) that usually only works for about 50% of patients. The radiation in this drug functions to destroy a portion of the thyroid gland. During this initial stage of drug therapy, the practitioner must monitor the patient carefully because the drug may induce bone marrow irregularities.

Complications after radioiodine treatment are relatively uncommon. The most notable complication is the development of hypothyroidism during the first year after treatment, which experts attribute to the fact that the iodine accelerates the natural progression of Graves' disease. Some of these patients may consequently require surgical removal of the thyroid gland.

The medical management of thyrotoxicosis resulting from hyperthyroidism involves the use of agents that block the synthesis of thyroid hormone. The most common agents used are propylthiouracil (PTU) and methimazole (Tapazole). Doctors generally recommend these medications for patients who exhibit mild cases of the disease and often use propranolol (Inderal) adjunctively to control symptoms such as tachycardia. Other management strategies aim at altering the autoimmune response via systemic corticosteroids, retrobulbar steroids, supervoltage orbital radiation, azathioprine, cyclophosphamide cyclosporine, plasma- pheresis and thyroid ablation.

In more recent years, physicians have increasingly turned to surgery as a primary treatment for hyperthyroidism. The chief advantages of doing so are that the treatment is permanent; surgical complications are rare; and surgery avoids the known risk of cancer associated with radioactive iodine treatment.

Your not-so-secret agents

Following is a comprehensive look at the medical agents you can use to treat thyroid disease.

Levothyroxine/Synthetic T4. This is one of the most commonly prescribed synthetic drug used in thyroid hormone replacement. See "Commonly Pre-scribed Thyroid Agents" on page 33 for a list of generic and brand name mediations. Levothyroxine provides a synthetic version of T4 to supplement what the body is unable to make on its own. This single agent is sufficient for many patients to adequately manage their condition.

Liothyronine/Synthetic T3. In addition to managing hypothyroidism with levothyroxine, some practitioners prefer to use a combination approach of levothyroxine plus an additional drug, liothyronine. The theory here is that impaired conversion of T4 to T3 may create a deficiency in T3 that warrants direct T3 supplementation, hence the need for the dual therapy. However, this combination approach is still controversial because many practitioners feel that patients don't need T3 because the body will convert T4 into the T3 based on the individual's metabolic needs.

Natural thyroid. Natural thyroid is dessicated thyroid, derived from pig glands. This was the agent of choice as the standard thyroid drug until levothyroxine entered the market in the second half of the 20th century. Many osteopathic and holistic ophthalmologists still like to use these natural drugs because they believe that the drug more closely mimics the human thyroid hormone as it contains a full spectrum of thyroid hormones.

Thyrotropin alfa. This agent is a special thyroid hormone replacement drug specifically intended for use in thyroid cancer patients who are going to undergo a thyroid scan or thyroglobulin test. Practitioners use this agent as short-term therapy immediately before testing. Typically, these patients have had to go off levothyroxine therapy and have suffered from severe hypothyroidism for the tests to be accurate. Thyrotropin alfa allows for accurate testing without the symptoms of hypothyroidism.

Antithyroid drugs. Two types of antithyroid drugs are available:

1. Methimazole

2. Propylthiouracil. Doctors use antithyroid drugs to treat hyperthyroidism -- and typically only for finite periods of time. If after a certain time period, the hyperthyroidism hasn't gone into remission, consider other treatments, such as radioactive iodine or surgery.

It reflects well on us

We often see patients with ocular manifestations of thyroid disease. Many times -- especially in newly diagnosed or undiagnosed cases -- this involves communication with the patient's primary care physician. By better understanding the overall diagnostic and management criteria for the systemic aspects of the disease, we can more effectively represent our profession.

References available on request

Dr. Gupta practices full scope optometry in Stamford, Conn. He's also clinical director of The Center for Keratoconus at Stamford Ophthalmology. E-mail him at Deegup4919@hotmail.com.

Ms. Gupta is a clinical pharmacist who has years of both retail and hospital pharmacy experience.