THE THYROID CLINIC

Thyroid disease, responsible for a spectrum of pathology from subclinical hormonal abnormalities to life-threatening disease, is easily and effectively treated. Between 5.9% and 11.7% of the population has abnormal values on thyroid screening. Hypothyroidism is 5 to 10 times as prevalent as thyrotoxicosis; symptomatic disease is found in 5% to 10% of patients with abnormal laboratory values. Thyrotoxic patients more commonly manifest clinical symptoms. 

Thyroid Physiology

Thyroid-stimulating hormone (TSH), secreted by the anterior pituitary gland, controls the synthesis and secretion of the thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Regulation of TSH levels is controlled by two mechanisms. The first is classic negative feedback to serum thyroid hormone concentration. Large inverse changes in TSH levels are precipitated by small changes in free thyroid hormone concentrations. Secondly, TSH concentration is regulated by the hypothalamic hormone thyrotropin-releasing hormone (TRH). The systems are interrelated in that the negative feedback of thyroid hormone probably affects TRH release from the hypothalamus in addition to TSH release from the pituitary. Thyroid-releasing hormone secretion is also affected by input from higher cortical centers. This system of thyroid hormone production is referred to as the hypothalamic-pituitary-thyroid axis.

At the molecular level, T4 is actually a prohormone and T3 is the biologically active chemical. All T4 is synthesized within the thyroid gland, whereas only 15% to 20% of T3 is synthesized directly. T4 is converted to T3 in peripheral organs, including the kidneys and liver. Thyroglobulin is a thyroid-hormone-containing protein stored in the colloid within thyroid follicles. T4 synthesis occurs within these follicles. Dietary iodide is trapped, oxidized, and combined with tyrosine residues. Coupling of these iodotyrosines produces T4. In healthy patients, about 41% of T4 is metabolized to T3 and 38% converts to RT3. 

The daily requirement for thyroid hormone is less than 1% of the amount stored within the gland, allowing maintenance of normal function when a person is deprived of iodine. The excess capacity, however, creates a vulnerability to thyrotoxicosis when the thyroid gland becomes inflamed and excess thyroid hormone is released .

Free T3 (FT3) and free T4 (FT4) serum levels provide more valuable clinical information. Thyroid-stimulating hormone secretion rhythmically varies between day and night. More than half is secreted in pulsatile fashion between 10:00 p.m. and 4:00 a.m. Sleep deprivation increases pulses, whereas sleep diminishes the pulses. The TSH molecules secreted at night demonstrate less hormonal activity than do daytime molecules. Therefore, there is no nocturnal surge in thyroid hormone levels in response to the increased secretion of TSH.

Hypothyroidism

The term hypothyroidism encompasses a broad spectrum of disease. Hypothyroidism can be congenital or acquired, primary or secondary, overt or subclinical, and goiterous or nongoiterous. Primary hypothyroidism, caused by thyroid gland failure, is responsible for more than 95% of cases of hypothyroidism. Low TSH or TRH levels from pituitary or hypothalamic failure cause central hypothyroidism, a relatively rare condition.

In areas of the world where iodine deficiency is unusual, most cases of primary hypothyroidism are associated with Hashimoto’s thyroiditis. Also known as chronic autoimmune thyroiditis, this disease is characterized by lymphocytic infiltration of the thyroid gland and the presence of antibodies directed against the TSH receptor, thyroperoxidase (TPO), and thyroglobulin. The TSH-receptor antibodies target a different area of the receptor than those found in patients with Grave’s disease; these antibodies block the action of TSH rather than stimulate the gland. Seven of 10 patients with Hashimoto’s thyroiditis are women, and the incidence increases with age. The disease assumes goiterous and atrophic forms; patients with goiter are usually asymptomatic but sometimes have thyroid tenderness not responsive to steroids.

Less common causes of hypothyroidism are listed in the tables below. The initial thyrotoxicosis seen in thyroiditis is often followed by a period of transient hypothyroidism. Iodine deficiency is the most common cause of hypothyroidism and goiter worldwide; it is rare in the United States due to the iodination of table salt. Paradoxically, iodine excess can also cause hypothyroidism: it inhibits the organification of iodine and the synthesis of T3 and T4 (the Wolff-Chaikoff effect).

Differential Diagnosis of Hypothyroidism

	Mechanisms	TSH	FT4, FT3
Primary hypothyroidism
Hashimoto’s disease	Autoimmune disease	High	Low
Surgical thyroidectomy	Iatrogenic	High	Low
External radiation	Iatrogenic	High	Low
Amyloidosis	Infiltrative	High	Low
Lymphoma	Infiltrative	High	Low
Scleroderma	Infiltrative	High	Low
Iodine deficiency or excess	Nutritional	High	Low
Drug-induced	Iatrogenic	High	Low
Secondary hypothyroidism
Sheehan’s Syndrome	Pituitary infarction	Low	Low
Pituitary neoplasm	Infiltrative/malignant	Low	Low
Pituitary radiation/surgery	Iatrogenic	Low	Low
Tertiary hypothyroidism
Sarcoidosis	Hypothalamic infiltration	Low	Low
Hypothalmic neoplasm	Malignancy	Low	Low

Methimazole and propylthiouracil decrease thyroid hormone secretion and are used therapeutically to treat hyperthyroid conditions. Drugs used for non-thyroid conditions that can cause clinical hypothyroidism include amiodorone, lithium, alfa-interferon, and interluekin-2. Lithium interferes with thyroid hormone synthesis and secretion: more than 50% of patients receiving long-term lithium therapy develop a goiter, and 12% develop clinical hypothyroidism. Amiodorone has caused both hyperthyroidism and hypothyroidism; the rate of both disorders is approximately 6 times higher in patients taking amiodorone than in those on other antidysrhythmics.

Clinical manifestations of hypothyroidism are the consequence of two basic physiologic effects of the lack of thyroid hormone: generalized slowing of metabolic processes and tissue deposition of glycosaminoglycans. Clinical manifestations of hypothyroidism with relative frequencies are listed in the following table. Because signs and symptoms of hypothyroidism are often nonspecific, develop insidiously, and can be mistaken for normal aging, clinical detection can be difficult. Accordingly, laboratory testing has assumed an increasingly important role in the detection of hypothyroidism.

Sensitivity and Specificity of the 14 Symptoms and Signs of Hypothyroidism 

Symptoms/Signs	Sensitivity (%)	Specificity (%)
Ankle reflex	77	93.5
Dry skin	76	63.8
Cold intolerance	64	65
Coarse skin	60	81.2
Puffiness	60	96.3
Pulse rate < 75/mina	58	42.5
Diminished sweating	54	86.2
Weight increase	54	77.5
Paraesthesia	52	82.5
Cold skin	50	80
Constipation	48	85
Slow movements	36	98.7
Hoarseness	34	87.5
Hearing impairment	22	97.5

 

Myxedema coma is a rare and potentially lethal complication of hypothyroidism. It is usually the result of acute decompensation in a patient with chronic hypothyroidism, often precipitated by stress such as infection, cold exposure, trauma, surgery, or stroke or the use of medications such as amiodorone and lithium. The condition is seen almost exclusively in women over 60 years of age and usually occurs during winter months. Contrary to the name, patients do not necessarily present with coma or oedema; clinical findings can include altered mental status, hypothermia, hypoventilation, hypotension, bradycardia, constipation, periorbital edema, nonpitting peripheral edema, and delayed relaxation of deep tendon reflexes. Associated abnormal laboratory findings can include anemia, hyponatremia, hypoglycemia, and elevated total creatinine kinase (CPK) levels. Myxedema coma can result in cardiovascular collapse; prompt recognition and treatment can be life saving.

Thyrotoxicosis and hyperthyroidism

Thyrotoxicosis refers to the increased metabolic and sympathetic nervous state that develops when serum concentrations of free thyroid hormone are elevated. One effect is increased sensitization to catecholamines. The terms thyrotoxicosis and hyperthyroidism are not synonymous. Hyperthyroidism, defined as thyroid gland hyperfunction, causes thyrotoxicosis due to increased thyroid hormone biosynthesis and release. Increased levels of thyroid hormone can occur, however, when thyroid gland function is normal. Examples include excess release of stored hormone from thyroid gland inflammation, excess exogenous thyroid hormone ingestion, and production of thyroid hormone from ectopic foci. Careful clinical evaluation complemented by appropriate laboratory investigation can clarify the specific aetiology of thyrotoxicosis.

Graves’ disease is the most common cause of hyperthyroidism in middle-aged patients and is the aetiology for 60% to 80% of all hyperthyroid patients. It is autoimmune in origin. Anti-TSH antibodies cause hyperstimulation of thyroid hormone and thyroid follicle hyperplasia. On physical examination, goiter, exophthalmos, and pretibial myxedema constitute the classic triad of Graves’ disease. Other causes of hyperthyroidism are listed below.

Differential Diagnosis of Thyrotoxicosis

	Mechanisms	RAI Uptake	TSH	FT4, FT3
Hyperthyroid etiologies
Graves’ disease	TSH receptor antibodies	High	Low	High
Toxic multinodular goiter	Multiple foci of autonomous thyroid function	High	Low	High
Toxic adenoma	Benign thyroid tumor with autonomous function	High	Low	High
Molar pregnancy	Greatly increased HCG levels stimulate TSH receptors	High	Low	High
Pituitary tumor	TSH hypersecretion	High	High	High
Pituitary resistance to thyroid hormone	Failure of normal feedback mechanism	High	High	High
Nonhyperthyroid etiologies
DeQuervain’s thyroiditis	Release of stored hormone	Low	Low	High
Postpartum thyroiditis	Release of stored hormone	Low	Low	High
Lingual goiter	Ectopic thyroid hormone secretion	Low	Low	High
Struma ovarii	Ectopic thyroid hormone secretion	Low	Low	High
Thyroid carcinoma	Ectopic thyroid hormone secretion	Low	Low	High
Jod-Basedow phenomenon	Iodine exposure secondary to radiologic studies	Low	Low	High
Chronic amiodarone use	Iodine exposure from amiodarone	Low	Low	High
Thyrotoxicosis facititia	Intentional thyroid hormone ingestion	Low	Low	High
Iatrogenic thyrotoxicosis	Excessive dose of thyroid hormone supplement	Low	Low	High

 

Patients with thyrotoxicosis without hyperthyroidism may present initially to the ED. Subacute or de Quervain’s thyroiditis classically presents with a tender thyroid gland, tachycardia, and flu-like symptoms. Multiple viruses have been linked to the disease. Physical examination reveals a tender and enlarged thyroid gland. The illness is self-limited and may be treated symptomatically with aspirin. More severe symptoms respond to prednisone. Beta blockers may be used to treat peripheral manifestations of thyrotoxicosis.

Subacute painless thyroiditis occurs in 2% to 6% of postpartum women in the United States. The usual time course is 3 to 6 months after delivery. It is likely the result of rebound immune activity. Fifty percent of patients manifest a firm painless goiter on physical examination. Thyrotoxic symptoms persist from 1 to 3 months. Beta blockade is effective symptomatic therapy . Clinical manifestations are precipitated by excessive release of thyroid hormone. Thyroiditis, a non-hyperthyroid condition, is differentiated from thyroid gland hyperfunction by measurement of radioactive iodine (RAI) uptake. Patients with hyperthyroidism will have high RAI uptake due to the increased glandular activity. Those with thyroiditis or exogenous thyroid ingestion will have low RAI uptake in the face of thyrotoxicosis.

Clinical Manifestations of Thyrotoxicosis

Organ System	Symptoms	Physical Findings
Cardiovascular	Palpitations	Sinus tachycardia
	Dyspnea	Atrial fibrillation
		Congestive heart failure
Dermatologic	Hair loss	Hair loss
		Warm, moist, smooth skin
		Palmar erythema
		Pretibial myxedema Onycholysis
Gastrointestinal	Increased appetite
	Weight loss
	Hyperdefecation
	Diarrhea
Gynecologic	Oligomenorrhea
	Amenorrhea
	Symptoms following pregnancy
Neuropsychiatric	Anxiety	Fine tremor
	Fatigue	Hyperreflexia
	Insomnia	Muscle wasting and weakness
	Irritability	Periodic paralysis
	Heat intolerance
Ophthalmologic	Feeling of grittiness	Exophthalmos
	Retrobulbar pressure	Conjunctival injection
	Diplopia	Ophthalmoplegia
Thyroid gland	Neck fullness	Thyroid enlargement
	Dysphagia

REFERENCE

Thyroid disease in the emergency department: A clinical and laboratory review
Journal of Emergency Medicine, Volume 28, Issue 2, February 2005, Pages 201-209
Laura Pimentel and Karen N. Hansen.

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