About Thyroid Disorders

Hypothyroidism and Hyperthyroidism
An estimated 108 million people in India suffer from endocrine and metabolic disorders. Several of these diseases are caused by environmental factors; therefore, their prevalence is several-fold higher. Thyroid disorders are the most common among all the endocrine diseases in India and hyperthyroidism and hypothyroidism are more frequent in women.1,2 Functional studies of the goitrous subjects showed overall prevalence of 5.4% hypothyroidism, 1.9% hyperthyroidism. 7.5% prevalence of autoimmune thyroiditis was demonstrable by fine needle aspiration biopsy.1

Hypothyroidism
Hypothyroidism refers to any state that results in a deficiency of thyroid hormone, including hypothalamic or pituitary disease and generalized tissue resistance to thyroid hormone, and disorders that affect the thyroid gland directly.2 The most common cause of hypothyroidism is primary failure of the thyroid gland. While secondary hypothyroidism from pituitary or hypothalamic dysfunction is rare, it is vital to identify the site of dysfunction at the outset. It covers a wide spectrum of clinical and biochemical disease, from clinically unapparent disease to myxoedema coma.3

Hypothyroidism, is a disease with wide ranging symptoms and signs affecting many systems.4 The signs and symptoms of hypothyroidism are nonspecific and may be confused with those of other clinical conditions, especially in postpartum women and the elderly. Patients with severe hypothyroidism generally present with a constellation of signs and symptoms that may include lethargy, weight gain, hair loss, dry skin, forgetfulness, constipation and depression. Not all of these signs and symptoms occur in every patient, and many may be blunted in patients with mild hypothyroidism.5

Hyperthyroidism
Clinically hyperthyroidism, also called thyrotoxicosis, is caused by the effects of excess thyroid hormone.6 Although the terms hyperthyroidism and thyrotoxicosis are frequently used interchangeably, in the strictest sense hyperthyroidism refers to hyper function of the thyroid gland, whereas thyrotoxicosis refers to any state characterized by thyroid hormone excess, including ingestion of excess thyroid hormone and thyroiditis.2

The cause of hyperthyroidism will differ between young and elderly patients. In young patients Graves's disease is the most common cause, whereas in elderly patients toxic nodular goiter is also a cause.2 Other causes include thyroiditis, toxic multinodular goiter, toxic adenomas, and side effects of certain medications.6

Hyperthyroidism presents with multiple symptoms that vary according to the age of the patient, duration of illness, magnitude of hormone excess, and presence of comorbid conditions. Older patients often present with a paucity of classic signs and symptoms, which can make the diagnosis more difficult.6 Signs and symptoms of hyperthyroidism include tremors, nervousness, insomnia, excessive sweating, heat intolerance, tachycardia, hypertension, and goiter.7

Thyroid storm is a rare presentation of hyperthyroidism that may occur after a stressful illness in a patient with untreated or undertreated hyperthyroidism and is characterized by delirium, severe tachycardia, fever, vomiting, diarrhea, and dehydration.6

References:
1. Kenneth A. Woeber, MD, FRCPE. Update on the Management of Hyperthyroidism and Hypothyroidism.
2. Duncan J Topliss and Creswell J Eastman. Diagnosis and management of hyperthyroidism and hypothyroidism.
3. Jayakumar RV. Hypothyroidism. J Indian Med Assoc. 2006 Oct;104(10):557-60, 562.
4. William JH. Treatment of Hypothyroidism. American family physician.
Available at: http://www.aafp.org/afp/20011115/1717.html
5. Reid JR, Wheeler SF. Hyperthyroidism: diagnosis and treatment. American family physician.
Available at: http://www.aafp.org/afp/20050815/623.html
Risk Factors
Hypothyroidism
Hypothyroidism may be congenital or acquired, primary or secondary, chronic or transient.1

Disease or treatments which destroy the thyroid gland or interfere with thyroid hormone biosynthesis are major risk factors associated with primary hypothyroidism. Autoimmune thyroiditis is the predominant risk factor of primary hypothyroidism. Another cause of primary hypothyroidism, chronic or transient, is previous radio-iodine or surgical treatment of hypothyroidism.

In secondary or central hypothyroidism, which is very rare, there is a lack of thyroid-stimulating hormone (TSH) or TSH activity, due to a pituitary or hypothalamic cause.1 Various types of medication, including amiodarone, cytokines and lithium, also often induce hypothyroidism.2
Other risk factors include: 3
. Atrophic thyroiditis
. Postpartum thyroiditis
. Iodine deficiency
. Scleroderma
. Thyroid ectopia
. Genetic disorders of TSH
. Thyroid hormone resistance
. Pituitary or hypothalamic disorders

Hyperthyroidism
Graves' disease is the most common risk factor of hyperthyroidism, accounting for 60 to 80 percent of all cases, which is an autoimmune disease caused by an antibody, active against the TSH receptor, which stimulates the gland to synthesize and secrete excess thyroid hormone.3 Other risk factors of hyperthyroidism are as follows:
. Multinodular goiter
. Thyroiditis (subacute, postpartum)
. Functioning thyroid carcinoma
. TSH- secreting pituitary tumour
. Partial thyroid hormone resistance
. Human chorionic gonadotropin (hCG) mediated
References:
1. Hallengren B. Hypothyroidism--clinical findings, diagnosis, therapy. Thyroid tests should be performed on broad indications.
Lakartidningen. 1998 Sep 16;95(38):4091-6.
2. Laurberg P, Andersen S, Bülow Pedersen I, Carlé A. Hypothyroidism in the elderly: pathophysiology, diagnosis and treatment.
Drugs Aging. 2005;22(1):23-38.
3. Reid JR, Wheeler SF. Hyperthyroidism: diagnosis and treatment. American family physician.
Available at: http://www.aafp.org/afp/20050815/623.html.
Clinical features
Hypothyroidism
As thyroid hormones are universal determinants of organ function, there may be a multiplicity of symptoms. Hypothyroidism emerges insidiously and is nonspecific. They include a general slowing down, mental depression, modest weight gain, intolerance of cold, constipation, vague aches and pains, dryness of the skin, and brittleness of the scalp hair.1
The clinical features of hypothyroidism are dependent on
. Patient's age
. Presence of other disease
. Rate at which hypothyroidism develops
The clinical features may be atypical, and the diagnosis may be missed easily particularly in the elderly.2

Once the disorder is fully established, the classic features of myxedema of the skin, periorbital edema, hoarseness, sinus bradycardia, decrease in body temperature, and delayed relaxation of the deep tendon reflexes appear. Laboratory investigation may reveal a mild anemia, increased creatine phosphokinase concentrations, and an abnormal lipid profile with increased total and low-density lipoprotein cholesterol and decreased high-density lipoprotein cholesterol concentrations.1 First line tests for hypothyroidism are analyses of the concentrations of free thyroxine (T4) and TSH in serum.2

Biochemical Markers in Hypothyroidism3
TSH level Free T4 level Free T3 level Likely diagnosis
High Low Low Primary hypothyroidism
High
(>10 µU per mL [10 mU per L])
Normal Normal Subclinical hypothyroidism with high risk for future development of overt hypothyroidism
High
(6 to 10 µU per mL [6 to 10 mU per L])
Normal Normal Subclinical hypothyroidism with low risk for future development of overt hypothyroidism
High High Low Congenital absence of T4-T3­converting enzyme; amiodarone (Cordarone) effect on T4-T3 conversion
High High High Peripheral thyroid hormone resistance
Low Low Low Pituitary thyroid deficiency or recent withdrawal of thyroxine after excessive replacement therapy
TSH = thyroid-stimulating hormone; T4 = thyroxine; T3 = triiodothyronine.
  • In primary hypothyroidism, the serum content of T4,T3 is low and that of TSH high
  • In central hypothyroidism, the serum content of T4,T3 is low and that of TSH generally low or normal, though slightly increased levels of biologically inactive TSH may also occur
  • Subclinical hypothyroidism is characterized by a normal serum level of T4,T3 an increased level of TSH, and the absence of clinical symptoms
Hyperthyroidism
The diagnosis of hyperthyroidism is suggested by the presence of a collection of symptoms and signs. In patients older than 70 years, however, the classic clinical manifestations may be lacking and goiter may be absent. Instead, anorexia with wasting, atrial fibrillation, or congestive heart failure may be the predominant manifestations. Furthermore, the cause of hyperthyroidism will differ between young and elderly patients. In young patients, Grave's disease is almost always the cause, whereas in elderly patients toxic nodular goiter (TNG) is also a common cause. 1

Clinical features of Hyperthyroidism4
Cause Pathophysiology Gland size Nodularity Tenderness
Toxic adenoma Autonomous hormone production Decreased Single nodule Nontender
Toxic multinodular goiter Autonomous hormone production Increased Multiple nodules Tender
Subacute thyroiditis Leakage of hormone from gland Increased None Tender
Lymphocytic thyroiditis, postpartum thyroiditis, medication-induced thyroiditis Leakage of hormone from gland Moderately increased None Nontender
Graves' disease (thyroid-stimulating antibody) Increased glandular stimulation (substance causing stimulation) Increased None Nontender
Iodine-induced hyperfunctioning of thyroid gland (iodide ingestion, radiographic contrast, amiodarone [Cordarone]) Increased glandular stimulation (substance causing stimulation) Increased Multiple nodules or no nodules Nontender
Functioning pituitary adenoma (thyroid-stimulating hormone); trophoplastic tumors (human chorionic gonadotropin) Increased glandular stimulation (substance causing stimulation) Increased None Nontender
Factitial hyperthyroidism Exogenous hormone intake Decreased None Nontender
Struma ovarii; metastatic thyroid cancer Extraglandular production Decreased None Nontender
TSH = thyroid-stimulating hormone; T4 = thyroxine; T3 = triiodothyronine.
References:
1. Kenneth A. Woeber, MD.Update on the Management of Hyperthyroidism and Hypothyroidism. Arch Intern Med. 2000;160:1067-1071.
2. Hallengren B. Hypothyroidism--clinical findings, diagnosis, therapy. Thyroid tests should be performed on broad indications.
Lakartidningen. 1998 Sep 16;95(38):4091-6.
3. Hueston WJ. Treatment of Hypothyroidism. Am Fam Physician. 2001 Nov 15;64(10):1717-1725.
4. Reid JR, Wheeler SF. Hyperthyroidism: Diagnosis and Treatment. Am Fam Physician. 2005 Aug 15;72(4):623-630
Co-morbidities
Co-morbid Conditions

Diabetes Mellitus: As diabetes mellitus type 1 is part of the polyglandular autoimmune syndrome, autoimmune disorders of the thyroid are also seen in diabetics about five times more common than in general population. Hypothyroidism leads to the decrease in insulin sensitivity and increase of glucose stimulated insulin secretion.1

Depression: Hypothyroid state is accompanied by anxiety/depressive symptoms.2 Cognitive deficits and depressive states are often found in overt hypothyroidism, psychotic derangements are rare. Psychic symptoms of hyperthyroidism include agitation, irritability, mood disturbances, hyperactivity, anxiousness and even panic attacks.3

Hypercholesterolaemia: Overt hypothyroidism is characterized by hypercholesterolemia and a marked increase in low-density lipoproteins (LDL) and apolipoprotein B. 90% of patients with hypothyroidism have hypercholesterolemia. Whereas, the prevalence of overt hypothyroidism in patients with hypercholesterolemia is estimated to be 1.3% to 2.8%, Lipid profile changes are also evident in subclinical hypothyroidism. Specifically, LDL is increased in subclinical hypothyroidism and reversible with thyroid hormone replacement.4

Infertility: Hypothyroidism in adults is associated with disturbances in the sex steroid hormone metabolism as well as infertility.5 About 25% female infertility and 15% menstrual cycle disorders result from thyroid dysfunction.6

Obesity: Thyroid dysfunction was found more in obese individuals with varying degree of significance.5 One of the studies showed that, overt hypothyroidism was present in 33% and subclinical hypothyroidism in 11% patients in obese patients.7

References:
1. Cáp J. Hypothyroidism substitution and adrenal insufficiency in diabetic patients. Vnitr Lek. 2009 Apr;55(4):371-4.
2. Constant EL, Adam S, Seron X, Bruyer R, Seghers A, Daumerie C. Hypothyroidism and major depression: a common executive dysfunction? J Clin Exp Neuropsychol. 2006 Jul;28(5):790-807.
3. Schmidt M, Huff W, Dietlein M, Kobe C, Schicha H. Interactions between brain, psyche and thyroid. Nuklearmedizin. 2008;47(6):225-34.
4. Klein I, Danzi S. Thyroid disease and the heart. Circulation. 2007 Oct 9;116(15):1725-35.
5. Krassas GE, Pontikides N. Male reproductive function in relation with thyroid alterations. Best Pract Res Clin Endocrinol Metab. 2004 Jun;18(2):183-95.
6. Maruna P. Gynecological aspects of thyroid disorders. A review. Ceska Gynekol. 2006 Jul;71(4):332-8.
7. Verma A, Jayaraman M, Kumar HK, Modi KD. Hypothyroidism and obesity. Cause or effect? Saudi Med J. 2008 Aug;29(8):1135-8.

End organ impact
Cardiovascular effects: Hypothyroidism is associated with mild increase in diastolic pressure and cardioembolic stroke.1 Hypothyroid patients, even those with subclinical hypothyroidism, have impaired endothelial function, normal/depressed systolic function, left ventricular diastolic dysfunction at rest, and systolic and diastolic dysfunction on effort, which may result in poor physical exercise capacity.2

Central nervous system: Hypo- or hyperthyroidism may result in an irreversible impairment, morphological and cytoarchitecture abnormalities, disorganization, malformations and physical retardation. This includes abnormal neuronal proliferation, migration, decreased dendritic densities and dendritic arborizations. This drastic effect may be responsible for the loss of neurons vital functions and may lead, in turn, to the biochemical dysfunctions.3

Skeletal system: Hypothyroidism causes impaired bone formation and growth retardation whereas thyrotoxicosis results in accelerated growth, advanced bone age and decreased bone mass. Adults with thyrotoxicosis or a suppressed thyroid stimulating hormone (TSH) from any cause have an increased risk of osteoporotic fracture.4

Gastrointestinal system: An increase in the incidence of thyroid disease has been reported in patients suffering from breast and colon cancer.5 Hypothyroidism is also one of the causes for constipation.6 Hyper- and hypothyroidism can impair esophageal motility, modifying pharyngo-esophageal structure and/or muscular function and interacting with the neuro-humoral regulation of the esophageal peristalsis.7

Renal system: Thyroid hormones (TH) are essential for an adequate growth and development of the kidney. Thyroid dysfunction causes remarkable changes in glomerular and tubular functions and electrolyte and water homeostasis. Hypothyroidism is accompanied by a decrease in glomerular filtration, hyponatremia, and an alteration of the ability for water excretion. Excessive levels of TH generate an increase in glomerular filtration rate and renal plasma flow.8

Skin: Nonpitting edema, generalized hair loss (especially along the outer third of the eyebrows), dry skin and a diminished relaxation phase of reflexes are usually associated with hypothyroidism.9

Reproductive system: Hypothyroidism in adults is associated with disturbances in the sex steroid hormone metabolism as well as infertility.10 About 25% female infertility and 15% menstrual cycle disorders result from thyroid dysfunction.11

References:
1. Klein I, Danzi S. Thyroid disease and the heart. Circulation. 2007 Oct 9;116(15):1725-35.
2. Biondi B, Klein I. Hypothyroidism as a risk factor for cardiovascular disease. Endocrine. 2004 Jun;24(1):1-13.
3. Ahmed OM, El-Gareib AW, El-Bakry AM, Abd El-Tawab SM, Ahmed RG.Thyroid hormones states and brain development interactions.
Int J Dev Neurosci. 2008 Apr;26(2):147-209. Epub 2007 Oct 12.
4. Galliford TM, Murphy E, Williams AJ, Bassett JH, Williams GR. Effects of thyroid status on bone metabolism: a primary role for
thyroid stimulating hormone or thyroid hormone? Minerva Endocrinol. 2005 Dec;30(4):237-46.
5. Syrigos KN, Konstantoulakis MM, Constantoulakis M, Marafelia P, Koutras D, Golematis BC.
Thyroid autoantibodies and thyroid function in patients with gastric cancer. Acta Oncol. 1994;33(8):905-7.
6. Lennard-Jones JE. Clinical management of constipation. Pharmacology. 1993 Oct;47 Suppl 1:216-23.
7. Pustorino S, Foti M, Calipari G, Pustorino E, Ferraro R, Guerrisi O, et al. Thyroid-intestinal motility interactions summary.
Minerva Gastroenterol Dietol. 2004 Dec;50(4):305-15.
8. Iglesias P, Díez JJ. Thyroid dysfunction and kidney disease. Eur J Endocrinol. 2009 Apr;160(4):503-15. Epub 2008 Dec 18.
9. Hueston WJ. Treatment of Hypothyroidism. Am Fam Physician. 2001 Nov 15;64(10):1717-1725.
10. Krassas GE, Pontikides N. Male reproductive function in relation with thyroid alterations. Best Pract Res Clin Endocrinol Metab.
2004 Jun;18(2):183-95.
11. Maruna P. Gynecological aspects of thyroid disorders. A review. Ceska Gynekol. 2006 Jul;71(4):332-8.
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