Thyroid and Mental Health

Contents

General Overview of the Thyroid

Disorders of the Thyroid

Lab Tests

Medications

Effects on Mental Health

References and Additional Resources

General Overview of the Thyroid

The thyroid gland is a small, soft, butterfly-shaped gland located in the anterior portion of the neck just below the larynx. A healthy thyroid converts iodine into thyroid hormones.

The two main hormones it produces is triiodothyronin, aka T3, and thyroxine, aka T4. These hormones regulate the rate of metabolism and affect the growth and rate of function of multiple other systems in the body.

T4, is considered a pro-hormone and eventually gets converted to T3, when it passes through the liver and kidneys, which is more active and is responsible for most metabolic effects.

Once thyroid hormones are released into the circulation, most of them circulate bound to protein. Approximately 70% of T3 and T4 are bound to thyroid-binding globulin.

The thyroid also contains the body's largest pool of iodine in the form of diiodotyrosine and monoiodotyrosine. Normally, in a healthy thyroid, this pool of iodine turns over slowly, about 1% per day.

Dysfunction and anatomic abnormalities of the thyroid are among the most common diseases of the endocrine glands. An individual whose thyroid function is normal is said to be in a euthyroid state.

Disorders of the Thyroid - Hypo

Hypothyroidism is the underproduction of the thyroid hormones T3 and T4. Typical symptoms are abnormal weight gain, tiredness, baldness, cold intolerance, and bradycardia.

Hypothyroidism can be caused in a variety of ways. They are classed into 3 types: Primary, Transient, and Secondary.

Primary hypothyroidism can be autoimmune, irradiation of the neck, sub or total thyroidectomy with no subsequent follow-up treatment, and iodine deficiency. In other words, causes created by the thyroid itself. Transient hypothyroidism is temporary and can be caused in the interim of a thyroidectomy before follow-up replacement therapy is commenced. Lastly, Secondary hypothyroidisn can be caused by hypopituitarism, Isolated TSH deficiency, or hypothalamic disease. Simply, causes created outside the thyroid that directly affects it.

Cretinism is a hypothyroid disorder that occurs in newborn infants. It can happen either postnatally or as a hereditary thyroid disease. It is the most frequent, preventable, and treatable metabolic defect in infants. Treatment for this disorder is thyroid replacement hormones.

Signs and symptoms are not usually recognized at birth but become apparent after a few weeks. On average, the diagnosis comes between 6-12 months. Untreated, the child becomes severely mentally disabled but placid. These children tend to sleep for much longer periods than normal children. Motor reflexes and movement become delayed.

Hashimoto's Thyroiditis is an autoimmune disorder in which the thyroid gland is destroyed by a variety of cell and antibody-mediated immune processes. Often it results in hypothyroidism with bouts of hyperthyroidism, thus leading sometimes to a misdiagnosis of bipolar disorder.

An average of 1 in 1000 people have this disease. It occurs 10 times more often in women than in men, and is most prevalent between the ages of 45-65 years.

Myxedema Coma is a severe hypothyroid state where the patient is increasingly withdrawn, lethargic, sleepy, and confused. This state can occur with or without a coma. It is usually associated with discontinuation of thyroid replacement post a thyroidectomy. It can also be precipitated by a CVA, heart attack, or something as small as a UTI.

Sick Euthyroid Syndrome or Nonthyroidal Illness is a state where an acute or chronic illness not affecting the thyroid, affects either the production of hormones or the ability to utilise the available hormones. More often than not, they present with euthyroid blood results.

Treatment of this illness with thyroid hormone replacement or not is usually left up to the attending doctor as the state can be quite acute or chronic depending on what the primary cause was.

Disorders of the Thyroid - Hyper

Hyperthyroidism is when the thyroid produces and secretes excessive amounts of the thyroid hormones.

Graves Disease is the most common cause of hyperthyroidism and accounts for 60-90% of all cases. It usually presents itself during early adolescence and can be inherited. It affect up to 2% of the population and is 10 times more common in females than in males.

The onset of Graves Disease symptoms is often insidious. The intensity of symptoms builds up with time and it can take months or even years before the patient is diagnosed with Graves. Only two symptoms are truly diagnostic of Graves. These are the protrusion of the eyes and pretibial myxedema, which is a rare skin disorder with an occurance rate of 1-4% that causes lumpy, reddish skin on the lower legs.

Treatment with antithyroid medications must be given 6 months-2 years, in order to be effective. However, reoccurance is high post cessation of the medication. Post medication treatment, thyroidectomy and radioiodine are considered in treatment.

Toxic Multinodular Goitre, also known as Plummer Disease, is the second most cause of hyperthyroidism. It usually occurs in older patients with long-standing multinodular goitres. The mangement of toxic nodular goitre may be difficult due to the patients age and possible other comorbidities. Control of the disease through antithyroid drugs, followed with radioiodine therapy is the preferred choice of treatment. Thyroidectomy is only contemplated if the patient is a good candidate for surgery.

Thyrotoxic Crisis (Thyroid Storm) is a rare complication of hyperthyroidism. It occurs in severely hyper patients who become very sick or physically stressed as well. This condition requires immediate hospitalization and treatment as it can quickly lead to coma and death.

Lab Values

Most abnormalities in thyroid function can be tested with a simple blood test.

In typical tests, hypothyroidism is characterized by an elevated TSH and decreased levels of T3 and T4. Conversely, hyper thyroidism is characterized by decreased TSH and elevated levels of T3 and T4. The antibody titres aren't routinely done unless there is a strong suspicion for autoimmune disorders of the thyroid.

In unclear and extreme cases, scans using radioactive iodine can be done to measure the thyroid's uptake ability. But as discussed earlier, thyroid issues can be cause by sources other than the thyroid itself and thus this result can also be unclear.

Medications

There are many medications that are typically used in treating both hypo and hyper states. In Australia, there are 4 main drugs used.

Eutrosig, or Oroxine dependant on the brand you get, is simply a thyroxine replacement. Effectiveness of this drug is dependant on a number of rules that most who take this drug learn quickly.

To ensure the thyroxine within the tablet remains viable, tablets must be refridgerated. A blister of thyroxine tablets can live outside of the fridge for up to 4 weeks. Post this period, tests have show that bacteria grow on the tablet, along with the deterioration of the contained thyroxine to sub-optimal levels.

Along with this, those on Eutrosig must take the tablet either at least an hour before food. If taken after food, it must be taken 3 hours after but wait another hour before eating again. This is due to food imparing the absorption rate of Eutrosig.

Tetroxin, also known as Liothyronine, is another replacement hormone. It's effect is similar to thyroxine but the effect develops more rapidly and disappears with 24-48 hours after stopping treatment. It is commonly used in the treatment and management of patients with Myxedema coma.

PTU, or propylthiouracil, is an antithyroid agent that blocks the peripheral comversion of T4 to T3 by inhibiting incorporation of iodine into tyrosine.. It is rapidly absorbed and has a half-life of 2 hours. Clinical response to the drug is usualy seen after a week of treatment, and stability of the patient to euthyroid status usually occurs 4-6 weeks after commencement of treatment.

Lastly, Neo-Mercazole, or Carbimazole, is another antithyroid agent that does the same as propylthioracil but doesn't inhibit the uptake of iodine into the thyroid which is important if the patient is undergoing radioactive iodine treatment.

There are others that are used overseas and also tentatively in Australia as well but we'd be here all day if I went through those as well.

With these four drugs, there has been many documented cases of interactions between thyroid medications, in particular the hypothyroid replacements, and mental health medications.

In particular, many commonly used psychotropic drugs such as Lithium, Epilim, Quetiapine, and Mirtazapine have been researched and found to change the effectiveness of hypothyroid drugs by interfering with the thyroid physiology and synthesis of thyroid hormones.

Lithium, given as a treatment for bipolar disorder and as an add-on to antidepressants in depression, can further complicate the association between affective disorders and the hypothalamic-pituitary-thyroid homeostasis because lithium itself can induce changes in this balance.

It has been well documented also that the prevalence of hypothyroidism in elderly patients with a affective disorder is not different from the general population, but the prevalence is high in elderly patients with an affective disorder on lithium treatment, especially in women.

Amongst other mood stabilizers, carbamazepine and valproate have been assessed to increase the risk of hypothyroidism amongst patients with bipolar disorders.

In a recent prospective double-blind study, a group of 30 schizophrenic patients taking quetiapine, risperidone, or fluphenazine showed a significant decrease in T4 levels after 6 weeks of treatment in the group recieving quetiapine, whereas other patients recieving risperidone and fluphenazine had no change in their thyroid hormone.

In another prospective study were 17 patients were taking 200mg/d od setraline or 40mg/d of fluoxetine over a 10-wk period, T3 and T4 levels were significantly decreased, whereas TSH levels didn't change.

In a prospective study evaluating the effects of mirtazapine on thyroid hormones in a small sample of 17 depressed outpatients, a significant increase of free T3 concentrations was found, whereas free T4 concentrations decreased after a 6-month follow-up period.

Effects on Mental Health

Abnormalities with the thyroid gland can mimic both manic and depressed presentations in mental health.

In general, hypothyroidism presents with depressed, fatigued, and lethargic appearance. Amotivation and loss of interest in activities can also result. Hyperthyroidism is the opposite end of the scale. It can present with anxious, agitated, irritable and aggressive appearances. Restlessness and hyperactivity can also appear.

Myxedematous Psychosis, or more commonly known as Myxedema Madness, is an uncommon side effect of prolonged hypothyroidism. A chronic and untreated underactive thyroid can slowly lead to dementia, delirium, and in extreme cases, hallucinations, coma, or psychosis, particularly in the elderly. In young children, it can stunt growth and brain development as well leaving the child mentally disabled.

Treatment is for this state is the same as for diagnoses hypothyroidism, with thyroid hormone replacement. Hormone replacement in these patients usually reverses the psychotic symptoms but cognitive deficits will remain due to the changes created in metabolic activity in the central nervous system.

Postpartum psychosis, an aspect of Postpartum Autoimmune Thyroid Disease, occurs in 0.1% of childbearing women. Symptoms include fluctuations in mood, delusions, hallucinations, agitation, insomnia, and cognitive impairment. It usually occurs within the first year after delivery.

Women with bipolar affective disorder are at high risk of developing postpartum psychosis. Up to half relapse early in the postpartum period, often with psychotic symptoms.

Lithium is used to manage this however, as discussed earlier, has the potential to worsen thyroid function.

Additional Information

As mention in the reference list, in Australia, we have the dedicated Thyroid Foundation who gain awareness through two important events:

Thyroid Awareness Week - 1st-7th June 2012 (first week in June yearly)

Golden Bow Day (Thyroid Cancer Awareness) 1st September

This is the symbol of the Australian Thyroid Foundation. The two loops of the bow symbolise the two lodes of the thyroid gland, one on either side of the neck. The gold colour symbolises that your thyroid is more valuable to you than gold.

More information can be found on their website.

www.thyroidfoundation.com.au

References

- Concise Pathology, 3rd Edition . Chapter 58: The Thyroid Gland . 1998, Appleton & Lange

- www.thyroidfoundation.com.au . 2011, The Australian Thyroid Foundation

- "Thyroid", "Graves Disease", "Thyroiditis", "Toxic Multinodular Goitre", "Myxedema", "Myxedematous Psychosis", "Hashimoto's Thyroiditis", "Hypothyroidism", "Hyperthyroidism" . 2012, Wikipedia

- "Eutrosig", "Propylthiouracil", "Carbimazole", "Tertroxin" . 2012, MIMS

- Endocrine Physiology, 3rd Edition . Chapter 4: Thyroid Gland . McGraw-Hill Co, 2009

- Thyroid Hormones Affect Recovery from Depression during Anti Depressant Treatment . Psychiaty and Clinical Neurosciences, Vol 63, 2009 pg 305-313

- Thyroid Disorders in Mental Patients . Current Opinion in Psychiatry, Vol 22, 2009 pg 391-395

- Prevalence and Determinants of Thyroid Disorders in Elderly Patients with Affective Disorders: Lithium and Nonlithium Patients . American Association for Geriatric Psychiatry, Vol 18, 2010 pg 395-403

- Thyroid Adverse Effects of Psychotropic Drugs: A Review . Clinical Neuropharmacology, Vol 34, 2011 pg 243-255

- Association Between Mood Stabilizers and Hypothyroidism in Patients with Bipolar Disorders: A Nested, Matched Case-Control Study . Bipolar Disorders, Vol 12, 2010 pg 253-263

- Thyroid Disease and Mental Disprders: Cause and Effect or only Comorbidity? . Current Opinion in Psychiatry, Vol 23, 2010 pg 363-368

- Thyroid Hormones and Depression: The Health in Men Study . American Journal of Geriatric Psychiatry, Vol 19, 2011 pg 763-770

- Prevalence of Autoimmune Thyroid Dysfunction in Postpartum Psychosis . British Journal of Psychiatry, Vol 198, 2011 pg 264-268

- Greenspan's Basic and Clinical Endocrinology, 9th Edition . Chapter 7: The Thyroid Gland . McGraw-Hill Co, 2009

- Hazzard's Geriatric Medicine and Gerontology, 6th Edition . Chapter 108: Thyroid Diseases . McGraw-Hill Co, 2009

- Adams and Victor's Principles of Neurology, 9th Edition . Chapter 40: The Acquired Metabolic Disorders of the Nervous System . McGraw-Hill Co, 2009