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Hypothyroidism

Hypothyroidisms

Hypothyroidism is a common disorder resulting from deficiency of thyroid hormone. Iodine deficiency is the most common cause of hypothyroidism worldwide. It can be associated with a number of symptoms including fatigue, weight gain, decreased appetite, cold intolerance, bradycardia, dry skin, hair loss, myalgia, depression, mental impairment, constipation, menstrual disturbances and impaired fertility. Myxedema coma, the most severe form of hypothyroidism, is rare.


Presentation

Hypothyroidism presents with the following signs and symptoms:

Cardiovascular

The heart muscle slows down and contractility decreases therefore the cardiac output is also decreased. Bradycardia, decreased systolic and increased diastolic blood pressure, systemic hypotension and in some severe cases, pericardial effusion may occur.

Urogenital

In females, menstrual abnormalities occur like amenorrhea and dysmenorrhea. Fertility is impaired.

Musculoskeletal

There is lethargy and generalised muscular and joint pain. Weakness of upper and lower extremities is also sometimes found. There is pitting or non pitting edema in extremities.

Nervous

Headaches, paresthesia and forgetfulness are common. Impaired memory, altered mental status and depression may occur in severe cases.

Gastrointestinal

Intestinal and gastric stasis, constipation and decreased appetite are common symptoms.

Eye

Blurred vision due to periorbital edema and puffing may occur.

Others

Hair turns coarse and brittle, skin becomes dry and pale, alopecia, weight gain, and cold intolerance and sleepiness are common presentations.

Complications are rare but may include infertility, fatal pericardial effusion and sudden hypotension leading to shock.

Hoarseness
  • A 40 year-old male presented with the history facial puffiness, hoarseness of voice and gait-ataxia. Investigations revealed frank primary hypothyroidism. Anti-TPO antibody was positive.[ncbi.nlm.nih.gov]
  • Hypothyroidism symptomatology was similar in both groups, except for a greater frequency of hoarseness in the group with HAH. Migraine history was more frequent in the patients with HAH (53% vs 38%, p   0.05).[ncbi.nlm.nih.gov]
  • She presented to our hospital with sudden-onset general malaise, edema, and hoarseness with an elevated thyroid-stimulating hormone (373.3 μIU/ml) level and very low triiodothyronine (  0.26 pg/ml) and thyroxine (0.10 ng/ml) levels.[ncbi.nlm.nih.gov]
  • (adolescent hypothyroidism) symptoms: Slow growth Delayed tooth development Tiredness Feeling cold Constipation Slow growth Delayed puberty Hoarse voice Slow speech Droopy eyelids Puffy and swollen face Hair loss Dry skin Slow pulse Weight gain (modest[stanfordchildrens.org]
  • Hypothyroidism signs and symptoms may include: Fatigue Increased sensitivity to cold Constipation Dry skin Weight gain Puffy face Hoarseness Muscle weakness Elevated blood cholesterol level Muscle aches, tenderness and stiffness Pain, stiffness or swelling[mayoclinic.org]
Fatigue
  • BACKGROUND Muscular symptoms, including stiffness, myalgia, cramps, and fatigue, are present in the majority of the patients with symptomatic hypothyroidism, but rhabdomyolysis, the rapid breakdown of skeletal muscle, is a rare manifestation.[ncbi.nlm.nih.gov]
  • By: Michael Lam, MD, MPH Adrenal Fatigue and Hypothyroidism The following table outlines the key differences in the signs and symptoms between Adrenal Fatigue and hypothyroidism symptoms.[drlam.com]
  • The usual clinical features are constipation, fatigue, cold intolerance and weight gain. Rarely it can present with neurologic problems like reversible cerebellar ataxia, dementia, peripheral neuropathy, psychosis and coma.[ncbi.nlm.nih.gov]
  • A 33 year-old, 8-week pregnant woman with hypothyroidism, presents with a 2-week history of palpitations, sweating, nervousness and fatigue. Physical examination shows tachycardia (108 bpm), distal tremors and diffuse goiter.[ncbi.nlm.nih.gov]
  • A Workout Plan for Hypothyroidism The right workout routine can help fight fatigue, weight gain, and other hypothyroidism symptoms. Start with these exercises.[everydayhealth.com]
Weight Gain
  • Others Hair turns coarse and brittle, skin becomes dry and pale, alopecia, weight gain, and cold intolerance and sleepiness are common presentations.[symptoma.com]
  • She was admitted to the tertiary care setup with the complains of cold intolerance, numbness in the limbs, high blood pressure & constipation, patient also had complain of weight gain, lab revealed high TSH, low Free thyroid hormones & positive anti thyroglobulin[ncbi.nlm.nih.gov]
  • The usual clinical features are constipation, fatigue, cold intolerance and weight gain. Rarely it can present with neurologic problems like reversible cerebellar ataxia, dementia, peripheral neuropathy, psychosis and coma.[ncbi.nlm.nih.gov]
  • The thyroid gets a bad rap, blamed for everything from fatigue to weight gain. weight gain with untreated hypothyroidism (and weight loss with treatment), get the go-ahead from your doctor before taking any medication while pregnant.[bernalheightsonline.com]
  • Patient II was a seven month old male infant with abdominal swelling, bilateral pitting leg oedema, poor weight gain and delayed developmental milestones. Examination revealed ascites and pericardial effusion.[ncbi.nlm.nih.gov]
Weakness
  • Within a week, he developed intermittent weakness of his left hand followed by intermittent weakness of both legs. On admission, he endorsed persistent dysarthria, generalized fatigue and improvement in extremity weakness.[neurology.org]
  • CASE REPORT We report a case of a 52-year-old Hispanic woman with a history of hypothyroidism, hypertension, and type 2 diabetes mellitus who presented with fatigue, severe generalized weakness, bilateral leg pain, and recurrent falls.[ncbi.nlm.nih.gov]
  • Weakness and aches are normal following strenuous activity. However, new, and especially increasing, weakness or aching is a good reason to make an appointment with your physician.[healthline.com]
  • It may also cause muscle weakness or loss of muscle control. Myxedema. This rare, life-threatening condition is the result of long-term, undiagnosed hypothyroidism.[mayoclinic.org]
  • The lack of energy and weakness I am experiencing at the age of 42 is maddening. I want my life back the way it was. I am tired of feeling tired and zombie like. A.[medical-dictionary.thefreedictionary.com]
Cold Intolerance
  • She was admitted to the tertiary care setup with the complains of cold intolerance, numbness in the limbs, high blood pressure & constipation, patient also had complain of weight gain, lab revealed high TSH, low Free thyroid hormones & positive anti thyroglobulin[ncbi.nlm.nih.gov]
  • The usual clinical features are constipation, fatigue, cold intolerance and weight gain. Rarely it can present with neurologic problems like reversible cerebellar ataxia, dementia, peripheral neuropathy, psychosis and coma.[ncbi.nlm.nih.gov]
  • It involves slowing of body functions, and symptoms include weight gain, dry skin, constipation, cold intolerance, puffy skin, hair loss, fatigue, and menstrual irregularity in women.[labtestsonline.org]
  • They may include Fatigue Weight gain A puffy face Cold intolerance Joint and muscle pain Constipation Dry skin Dry, thinning hair Decreased sweating Heavy or irregular menstrual periods and fertility problems Depression Slowed heart rate To diagnose hypothyroidism[medlineplus.gov]
  • Others Hair turns coarse and brittle, skin becomes dry and pale, alopecia, weight gain, and cold intolerance and sleepiness are common presentations.[symptoma.com]
Hypothermia
  • Its characteristics include coma with extreme hypothermia (temperature 24 to 32.2 C), areflexia, seizures, and respiratory depression with carbon dioxide retention. Severe hypothermia may be missed unless low-reading thermometers are used.[merckmanuals.com]
  • Concurrent supportive therapy addresses precipitants such as infection, medications, and cerebrovascular disease as well as symptoms such as hypothermia and hypotension.[clinicaladvisor.com]
  • Myxedema coma is characterized by nonresponsiveness, low body temperature (hypothermia), and respiratory depression .[britannica.com]
  • Myxedema coma is a severe form of hypothyroidism that results in an altered mental status, hypothermia, bradycardia, hypercarbia, and hyponatremia. Cardiomegaly, pericardial effusion, cardiogenic shock, and ascites may be present.[emedicine.medscape.com]
  • Mental status changes including lethargy, cognitive dysfunction, and even psychosis, and hypothermia are the hallmark features of myxedema coma. 33 Hyponatremia, hypoventilation, and bradycardia can also occur.[aafp.org]
Constipation
  • She was admitted to the tertiary care setup with the complains of cold intolerance, numbness in the limbs, high blood pressure & constipation, patient also had complain of weight gain, lab revealed high TSH, low Free thyroid hormones & positive anti thyroglobulin[ncbi.nlm.nih.gov]
  • The usual clinical features are constipation, fatigue, cold intolerance and weight gain. Rarely it can present with neurologic problems like reversible cerebellar ataxia, dementia, peripheral neuropathy, psychosis and coma.[ncbi.nlm.nih.gov]
  • While constipation is a common complaint in patients with hypothyroidism, it's uncommon for constipation to be the only or most severe symptom ( 24 ).[healthline.com]
  • They may also have: Constipation Poor muscle tone Excessive sleepiness When hypothyroidism in infants isn't treated, even mild cases can lead to severe physical and intellectual disabilities.[mayoclinic.org]
  • Gastrointestinal Intestinal and gastric stasis, constipation and decreased appetite are common symptoms. Eye Blurred vision due to periorbital edema and puffing may occur.[symptoma.com]
Nausea
  • The HAH features were as follows: pulsatile (63%), four to 72 hours' duration (78%), unilateral (47%), nausea/vomiting (60%), and moderate-severe intensity (72%).[ncbi.nlm.nih.gov]
  • Side effects Common side effects may include: - anxiety - nervousness - depressive condition - insomnia - headache - dizziness During the first week of drug use the patient may also experience the following side effects: stomachache, nausea, diarrhea,[corpohs.com]
  • Signs of lactose intolerance include nausea, cramps, bloating, gas, and diarrhea. Usually, the symptoms will begin 30 minutes to 2 hours after taking your Synthroid pill.[everydayhealth.com]
Loss of Appetite
  • Drowsiness Appetite loss Ankle, feet, and leg swelling Short stature Separated sutures Delayed formation or absence of teeth Signs and tests: A physical examination reveals delayed relaxation of muscles during tests of reflexes.[uclahealth.org]
Palpitations
  • A 33 year-old, 8-week pregnant woman with hypothyroidism, presents with a 2-week history of palpitations, sweating, nervousness and fatigue. Physical examination shows tachycardia (108 bpm), distal tremors and diffuse goiter.[ncbi.nlm.nih.gov]
  • These include weight loss, persistent vomiting, and palpitations. Cant lose weight after pregnancy? It could be changes to your thyroid function that can occur after pregnancy.[bernalheightsonline.com]
  • Reactivity Heightened and hyper-reactive Hypo-reactive Medical condition History of Infections Common Occasional Chronic Fatigue Yes Yes Orthostatic Hypotension Frequent No Blood Sugar Levels Tendency toward hypoglycemia Normal to hyperglycemia Heart Palpitation[drlam.com]
  • While you are taking thyroid replacement therapy, tell your doctor if you have any symptoms that suggest your dose is too high, such as: Palpitations Rapid weight loss Restlessness or shakiness Sweating Outlook (Prognosis) In most cases, thyroid hormone[mountsinai.org]
  • However, over treating hypothyroidism with excessive thyroid medication is potentially harmful and can cause problems with heart palpitations and blood pressure control, and contribute to osteoporosis .[medicinenet.com]
Blurred Vision
  • Eye Blurred vision due to periorbital edema and puffing may occur. Others Hair turns coarse and brittle, skin becomes dry and pale, alopecia, weight gain, and cold intolerance and sleepiness are common presentations.[symptoma.com]
  • vision Decreased hearing Fullness in the throat, hoarseness Hashimoto thyroiditis is difficult to distinguish clinically, but the following symptoms are more specific to this condition: Feeling of fullness in the throat Painless thyroid enlargement Exhaustion[emedicine.medscape.com]
Muscle Cramp
  • Common symptoms and signs include: Fatigue Depression Modest weight gain Cold intolerance Excessive sleepiness Dry, coarse hair Hair loss Menstrual disturbances Mood changes Decreased perspiration Constipation Dry skin Muscle cramps Increased cholesterol[medicinenet.com]
  • Symptoms of Hypothyroidism Fatigue Weakness Weight gain or increased difficulty losing weight Coarse, dry hair Dry, rough pale skin Hair loss Cold intolerance (you can't tolerate cold temperatures like those around you) Muscle cramps and frequent muscle[endocrineweb.com]
  • cramps Sides of eyebrows thin or fall out Confusion Increased or irregular menstrual flow in women These symptoms may look like other health problems.[cedars-sinai.edu]
  • Symptoms may include: Fatigue and/or exercise intolerance Slower reaction time (an important issue for drivers) Weight gain Constipation Sparse, coarse and dry hair Coarse, dry and thickened skin Slow pulse Cold intolerance Muscle cramps Sides of eyebrows[chop.edu]
Myalgia
  • BACKGROUND Muscular symptoms, including stiffness, myalgia, cramps, and fatigue, are present in the majority of the patients with symptomatic hypothyroidism, but rhabdomyolysis, the rapid breakdown of skeletal muscle, is a rare manifestation.[ncbi.nlm.nih.gov]
  • It can be associated with a number of symptoms including fatigue, weight gain, decreased appetite, cold intolerance, bradycardia, dry skin, hair loss, myalgia, depression, mental impairment, constipation, menstrual disturbances and impaired fertility.[symptoma.com]
  • Dry skin, constipation, headaches, arthralgia, myalgia, paresthesia, and menorrhagia may also occur.[clinicaladvisor.com]
  • Common Symptoms of Hypothyroidism Arthralgias Cold intolerance* Constipation Depression Difficulty concentrating Dry skin Fatigue* Hair thinning/hair loss Memory impairment Menorrhagia Myalgias Weakness Weight gain Table 1.[aafp.org]
Arthralgia
  • Dry skin, constipation, headaches, arthralgia, myalgia, paresthesia, and menorrhagia may also occur.[clinicaladvisor.com]
  • Musculoskeletal symptoms (especially arthralgias) occur often, but arthritis is rare. Muscular aches and weakness, often mimicking polymyalgia rheumatica or polymyositis, and an elevated CK level may occur.[merckmanuals.com]
  • Common Symptoms of Hypothyroidism Arthralgias Cold intolerance* Constipation Depression Difficulty concentrating Dry skin Fatigue* Hair thinning/hair loss Memory impairment Menorrhagia Myalgias Weakness Weight gain Table 1.[aafp.org]
Dry Skin
  • Myxedema is more specific to thyroid problems than other causes of dry skin ( 16 ). Summary: Hypothyroidism commonly causes dry skin. However, most people with dry skin do not have hypothyroidism.[healthline.com]
  • It involves slowing of body functions, and symptoms include weight gain, dry skin, constipation, cold intolerance, puffy skin, hair loss, fatigue, and menstrual irregularity in women.[labtestsonline.org]
  • They may include Fatigue Weight gain A puffy face Cold intolerance Joint and muscle pain Constipation Dry skin Dry, thinning hair Decreased sweating Heavy or irregular menstrual periods and fertility problems Depression Slowed heart rate To diagnose hypothyroidism[medlineplus.gov]
  • skin, a pale, puffy face, constipation or a hoarse voice.[mayoclinic.org]
  • This causes the body’s system to slow down and can lead to symptoms like fatigue, feeling cold, weight gain due to fluid retention, dry skin, and hair loss. If you experience any of these symptoms, talk to your doctor.[synthroid.com]
Alopecia
  • Others Hair turns coarse and brittle, skin becomes dry and pale, alopecia, weight gain, and cold intolerance and sleepiness are common presentations.[symptoma.com]
  • Alopecia, weight gain, mental dullness, fatigue, cold intolerance, infertility and neurological deficits are seen. In food animals the syndrome is classical neonatal colloid goiter.[medical-dictionary.thefreedictionary.com]
  • In fact, the metabolism of zinc and thyroid hormones are closely interlinked, which is why a deficiency can lead to alopecia (hair loss) ( 7 ).[dietvsdisease.org]
Decreased Sweating
  • They may include Fatigue Weight gain A puffy face Cold intolerance Joint and muscle pain Constipation Dry skin Dry, thinning hair Decreased sweating Heavy or irregular menstrual periods and fertility problems Depression Slowed heart rate To diagnose hypothyroidism[medlineplus.gov]
  • Some common symptoms of hypothyroidism include fatigue weight gain a puffy face trouble tolerating cold joint and muscle pain constipation dry skin dry, thinning hair decreased sweating heavy or irregular menstrual periods fertility problems depression[niddk.nih.gov]
  • Classic signs and symptoms (eg, cold intolerance, puffiness, decreased sweating, and coarse skin) may not be present as commonly as was once believed. Many of the more common symptoms are nonspecific and difficult to attribute to a particular cause.[emedicine.medscape.com]
Emotional Lability
  • The following are symptoms of hypothyroidism: Fatigue, loss of energy, lethargy Weight gain Decreased appetite Cold intolerance Dry skin Hair loss Sleepiness Muscle pain, joint pain, weakness in the extremities Depression Emotional lability, mental impairment[emedicine.medscape.com]
  • According to medical references, levothyroxine can have side effects that affect mood including: anxiety, emotional lability (excessive emotional reactions and frequent mood swings), irritability, etc.[everydayhealth.com]
Lethargy
  • Musculoskeletal There is lethargy and generalised muscular and joint pain. Weakness of upper and lower extremities is also sometimes found. There is pitting or non pitting edema in extremities.[symptoma.com]
  • Definition (CSP) deficiency of thyroid gland activity; characterized by decreased basal metabolic rate, fatigue and lethargy, sensitivity to cold, and menstrual disturbances; untreated it progresses to myxedema; in infants severe hypothyroidism leads[fpnotebook.com]
  • Neuromuscular symptoms include slowing of thought, speech, and action; lethargy and fatigue ; sleepiness; muscle aches and weakness; and slow reflexes.[britannica.com]
  • Its signs and symptoms include intense cold intolerance and drowsiness followed by profound lethargy and unconsciousness. A myxedema coma may be triggered by sedatives, infection or other stress on your body.[mayoclinic.org]
  • Symptoms are intense sensitivity to cold and drowsiness or severe lethargy. This can lead to unconsciousness and a coma. See a doctor right away if you notice these warning signs. Birth defects.[familydoctor.org]
Difficulty Concentrating
  • Symptoms associated with hypothyroidism include: Fatigue Lack of energy or drive Daytime sleepiness Weight gain Water retention or bloating (also known as myxedema) Thinning hair Dry skin Constipation Difficulty concentrating It is very important to keep[columbiasurgery.org]
  • Summary: Hypothyroidism can cause mental fogginess and difficulty concentrating. It may also impair certain kinds of memory. Low thyroid levels put the brakes on your colon.[healthline.com]
  • Common Symptoms of Hypothyroidism Arthralgias Cold intolerance* Constipation Depression Difficulty concentrating Dry skin Fatigue* Hair thinning/hair loss Memory impairment Menorrhagia Myalgias Weakness Weight gain Table 1.[aafp.org]
  • Memory problems, depression, or difficulty concentrating. An inability to tolerate cold. Dry skin, brittle nails, or a yellowish tint to the skin. Constipation. Heavy or irregular menstrual periods that may last longer than 5 to 7 days.[northshore.org]
Paresthesia
  • Nervous Headaches, paresthesia and forgetfulness are common. Impaired memory, altered mental status and depression may occur in severe cases. Gastrointestinal Intestinal and gastric stasis, constipation and decreased appetite are common symptoms.[symptoma.com]
  • Dry skin, constipation, headaches, arthralgia, myalgia, paresthesia, and menorrhagia may also occur.[clinicaladvisor.com]
  • Metabolic manifestations: Cold intolerance, modest weight gain (due to fluid retention and decreased metabolism), hypothermia Neurologic manifestations: Forgetfulness, paresthesias of the hands and feet (often due to carpal tunnel syndrome caused by deposition[merckmanuals.com]
  • Sleepiness Muscle pain, joint pain, weakness in the extremities Depression Emotional lability, mental impairment Forgetfulness, impaired memory, inability to concentrate Constipation Menstrual disturbances, impaired fertility Decreased perspiration Paresthesias[emedicine.medscape.com]
Memory Impairment
  • Common Symptoms of Hypothyroidism Arthralgias Cold intolerance* Constipation Depression Difficulty concentrating Dry skin Fatigue* Hair thinning/hair loss Memory impairment Menorrhagia Myalgias Weakness Weight gain Table 1.[aafp.org]
  • See also Hashimoto's disease, myxedema . observations Manifestations include weight gain; cold, pale, dry, rough hands and feet; reduced attention span with memory impairment, slowed speech, and loss of initiative; swelling in extremities and around the[medical-dictionary.thefreedictionary.com]

Workup

A complete work up includes checking of functional hormone levels of first T3 and T4 to see if the hypothyroidism is primary. Then levels of TSH and TRH are examined to determine any secondary causes. The plasma levels of Anti-TPO antibodies are also evaluated to check for Hashimoto’s [5].

Dyslipidemia
  • Fenofibrate is a fibric acid derivative indicated for use in hypertriglyceridemia and mixed dyslipidemia treatment among adults.[ncbi.nlm.nih.gov]
  • Untreated hypothyroidism can contribute to hypertension, dyslipidemia, infertility, cognitive impairment, and neuromuscular dysfunction.[aafp.org]
  • Prevalence and correction of hypothyroidism in a large cohort of patients referred for dyslipidemia. Arch Intern Med . 1995 ; 155 : 1490–1495. Crossref Medline Google Scholar 93 Duntas LH. Thyroid disease and lipids. Thyroid . 2002 ; 12 : 287–293.[stroke.ahajournals.org]
Hypertriglyceridemia
  • Fenofibrate is a fibric acid derivative indicated for use in hypertriglyceridemia and mixed dyslipidemia treatment among adults.[ncbi.nlm.nih.gov]

Treatment

Primary hypothyroidism can be treated by treating the cause. Nutritional deficiency can be corrected by adjusting an adequate intake of Iodine in diet [7]. Systemic manifestations can be treated by giving Levothyroxine (LT4) between 50-75 micrograms daily for mild to moderate hypothyroidism [6]. Effects are usually seen within 3-6 days of treatment.

Myxoedema is treated by giving a 200-250 microgram dose intravenously at first and then levelled down to about 50 microgram/day, accompanied by intravenous glucocorticoids.

Prognosis

Initial Stage

Initially, there is a gradual decrease in hormone levels causing low metabolism. This results in features like lethargy, easy fatiguability, weight gain, bradycardia and hypotension. Then there is pitting edema in lower extremities, especially around the ankles, coarse brittle hair, skin pallor and dryness [9]. A goitre may develop.

Advanced Stage

In advanced stage of this condition, the goiter may become enlarged and sometimes toxic and nodular. There may be severe hypotension and massive weight gain, slow speech and movements, hyporeflexia, myxadematous nonpitting edema, pericardial effusion, periorbital swelling and infertility.

Etiology

The etiology of hypothyroidism can be broadly divided into primary, secondary and tertiary. Each category has various factors that predispose towards hypothyroidism.

Primary Hypothyroidism

This category consists of all such causes that deter the synthesis and/or secretion of thyroid hormones from the thyroid gland. It includes:

Iodine Deficiency Hypothyroidism

The most common cause of primary hypothyroidism worldwide is Iodine deficiency. Iodine is one of the basic building blocks of thyroid hormones. Required for the synthesis of T3 and T4, Iodine deficiency leads to hypertrophy and hyperplasia of the follicular cells creating a goitre.

Iodine Excess Hypothyroidism

An overload of Iodine causes a gradual inhibition of iodide organification occurring in the thyroid follicles. This effect, called the Wolff-Chiakoff effect can occur due to very high levels of Iodine in the blood caused by some radio contrast dyes, drugs like amiodarone, increased intake of seafood and seaweed, etc. the Wolff-Chiakoff effect is however, short lived due to the rapid down regulation by the sodium-iodide symporter[10].

Chronic Lymphocytic Hypothyroidism

This is an autoimmune condition and commonly known as Hashimoto's disease. In this disease, thyroid antigens are mistakenly taken as foreign by the immune system which then launches a full scale attack on thyroid follicles. The attacking antibodies cause a chronic immune response that leads to a build-up of a lymphocytic infiltrate and progressive damage and destruction of the gland parenchyma.
Circulating anti-thyroid peroxidase antibodies (Anti-TPO) are the hallmark of this disease.
Hashimoto's disease is the most common acquired cause of hypothyroidism in the United States as well as other countries where there is a normal intake of Iodine.

Sub acute Thyroiditis

Sub acute granulomatous thyroiditis is an uncommon, self-limiting disorder that usually affects middle aged females. It is a painful form of thyroiditis associated with viral infections leading to an increased ESR, fever and dysphagia. This disease is also known as Quatrain Disease.

Drug Induced or Iatrogenic Hypothyroidism

Many drugs are known to cause hypothyroidism if used for a prolonged period of time [1]. The most common drugs predisposing to hypothyroidism include:

  • Amiodarone
  • Lithium
  • Stavudine
  • Ethionamide
  • Interferon Alpha
  • Thalidomide
  • Phenobarbital
  • Rifampin
  • Carbamazepine
  • Para-amino salicylic acid
  • Phenytoin

Iatrogenic causes may include the use of radioactive iodine for the treatment of Grave's disease and exposure to radiation as part of treatment of cancers such as neck neoplasms, Hodgkin's lymphoma, salivary gland tumours, etc. Patients who have undergone thyroid lobectomy, which may or may not be accompanied with isthmectomy, have a 12-30% chance of developing hypothyroidism.

Postpartum Thyroiditis

After 2 months to about a year from delivery, about 10% women may develop thyroid insufficiency. This condition is usually transient and can be avoided and treated with levothyroxine but in some cases it may cause permanent hypothyroidism. Chances of developing postpartum thyroiditis is increased to about 25% in females with diabetes mellitus type I.

Secondary and Tertiary Hypothyroidism

The factors involved in this category are directly or indirectly involved in modifying the function of the thyroid gland. They include:

  • TSH deficiency
  • TRH deficiency or resistance
  • Sheehan syndrome
  • Pituitary and Hypothalamic tumours
  • Congenital non-goiterous hypothyroidism 
  • Drugs
  • Radiation damaging the hypothalamic-pituitary axis

TSH Deficiency

A deficiency in the Thyroid Stimulating Hormone secreted by the pituitary gland may cause improper functioning of the thyroid gland and decreased synthesis of T3 and T4 [4].

TRH Deficiency or Resistance

A deficiency in the hypothalamic Thyroid Releasing Hormone may cause none to low secretion of TSH from the pituitary gland and therefore, decreased production of thyroid hormones. TRH deficiency may arise due to an isolated mutation in the TRH gene, inherited in an autosomal recessive fashion. A defect in the TRH receptors on the pituitary, due to a mutation in the THRH gene, produces TRH resistance and it also gives the same results. TRH resistance is a very rare autosomal recessive disease.

Sheehan Syndrome

Sheehan syndrome, a postpartum complication in which pituitary cells are infarcted due to increased blood loss during delivery may lead to decreased production of TSH and therefore, T3 and T4.

Pituitary and Hypothalamic Tumours

Tumours in or around these two glands may impinge on and suppress the function of hormone secreting cells causing hypothyroidism.

Congenital Non-Goiterous Hypothyroidism Type 4

This autosomal recessive disease results in low TSH levels which remain low despite injecting TRH [3]. It is caused by a mutation in the TSHB gene.

Drugs and Radiation

Continuous use of some drugs like prednisone and dopamine as well as exposure to direct radiation may damage the hypothalamic-pituitary axis causing hypothyroidism, among other systemic manifestations.

Epidemiology

Hypothyroidism occurs worldwide.

Sex

It is more common in females, the female-to-male ratio being 10:1

Race

It is more prevalent in Caucasians than in Hispanics or Blacks.

Age

Hypothyroidism affects people of all ages. Primary hypothyroidism can occur at any age but a higher prevalence is found in patient over 65 years.

Sex distribution
Age distribution

Pathophysiology

Under normal conditions the thyroid gland releases around 100-125 nmol of T4 daily of which most is converted in the peripheral tissues into T3, the active form of the hormone. This conversion from prohormone to active hormone is due to 5' deiodination.
The active hormone, T3 now circulates in the blood and acts on various receptors causing a wide range of systemic and metabolic effects.

Due to an infection, glandular loss, autoimmune attack or iodine deficiency, or due to any other cause mentioned above, the synthesis of T4 is impaired. Decreased production and secretion of T4 leads to decreased levels of T3 in blood which is unable to act on all its receptors, producing systemic manifestations.

Effects of hypothyroidism include decreased heart contractility and cardiac output, increased insulin resistance, increased cholesterol levels particularly those of LDL. Effects in the gastrointestinal tract include achloroydia, decreased metabolic rate leading to gastric stasis, prolonged intestinal transit time and weight gain. Menstrual disturbances and infertility are common.

Prevention

Hypothyroidism can be prevented by taking adequate Iodine in diet and avoiding consanguineous marriages (in case of congenital hypothyroidism).

Summary

Hypothyroidism is a very common endocrine disorder in which the thyroid gland does not function properly. This results in a decreased production of the thyroid hormone which causes systemic defects and characteristic symptoms.

Hypothyroidism can be primary or secondary. Primary hypothyroidism is due to a defect in the thyroid gland itself causing decreased synthesis and secretion of thyroid hormones T3 and T4. This primary defect can be caused either by a deficiency in one or more of the building products of the hormones, most common of which is iodine, or it could arise from an infection in the gland's parenchyma.

Another factor which also happens to be one of the most common one is autoimmune where autoantibodies attack the thyroid gland and greatly disturb its functioning [2]. Whatever the underlying cause may be, the defect is clearly centred on the gland itself.

In the case of secondary or central hypothyroidism, the defect lies in an organ other than the thyroid gland. In this instance, the pituitary gland could be responsible as it could be releasing decreased levels of TSH or the hypothalamus may be at fault, for secreting low levels of TRH (the latter is sometimes categorised as tertiary hypothyroidism).

Whatever the cause may be, the resultant decrease of T3 and T4 hormones causes widespread effects.

Patient Information

Definition

Hypothyroidism is a disorder in which there is decreased or inadequate functioning of the thyroid gland leading to widespread effects.

Symptoms

The most common ones include decreased appetite, weight gain, and lethargy, swelling in the neck called goitre, decreased blood pressure, constipation, muscle pain and ankle swelling and menstrual abnormalities in females.

Prevention

The most common worldwide form of hypothyroidism can be prevented by taking adequate Iodine in diet [8].

Complications

If untreated, the disease may progress to infertility, heart defects, impaired memory and depression.

Treatment

Hormone replacement therapy successfully treats this disease.

References

Article

1. Wolter P, Dumez H, Schöffski P. Sunitinib and hypothyroidism. N Engl J Med. Apr 12 2007;356(15):1580; author reply 1580

2. Cetani F, Barbesino G, Borsari S, Pardi E, Cianferotti L, Pinchera A, et al. A novel mutation of the autoimmune regulator gene in an Italian kindred with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, acting in a dominant fashion and strongly cosegregating with hypothyroid autoimmune thyroiditis. J Clin Endocrinol Metab. Oct 2001;86(10):4747-52.

3. Doeker BM, Pfäffle RW, Pohlenz J, Andler W. Congenital central hypothyroidism due to a homozygous mutation in the thyrotropin beta-subunit gene follows an autosomal recessive inheritance. J Clin Endocrinol Metab. May 1998;83(5):1762-5.

4. Sawin CT, Castelli WP, Hershman JM, McNamara P, Bacharach P. The aging thyroid. Thyroid deficiency in the Framingham Study. Arch Intern Med. Aug 1985;145(8):1386-8.

5. Clinical guideline, part 1. Screening for thyroid disease. American College of Physicians. Ann Intern Med. Jul 15 1998;129(2):141-3.

6. Baskin HJ, Cobin RH, Duick DS, Gharib H, Guttler RB, Kaplan MM, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract. Nov-Dec 2002;8(6):457-69.

7. Gullo D, latina A, Frasca F, Moli RL, Pellegriti G, et al. Levothyroxine monotherapy cannot guarantee euthyroidism in all athyreotic patients. PLoS One 2011;6(8):e22552. Epub 2011 Aug 1.


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Last updated: 2018-06-22 10:43