Lecture_5

Lecture 5.

HYPOTHYROIDISM. THYROIDITIS. DIADNOSTIC CRITERIA.

TREATMENT.

Hypothyroidism (myxedema).

It is the characteristic reaction to thyroid hormone deficiency. The spectrum of hormone ranges from a few non – specific symptoms to overt hormone, to myxedema coma. Hypothyroidism occurs in 3 to 6 for the adult population, but is symptomatic only in a minor of them. It occurs 8 to 10 times more often in woman than in men and usually develops after the age of 30.

Classification

1.Congetial.

2.Acquired: 1. Primary (thyroid gland disturbances).

2.Secondary (due to pituitary disease).

3.Tertiary (due to hypothalamic disease). 4.Peripheral.

Etiology

A cause is usually evident from the history and physical examination.

1.Primary (thyroidal) hypothyroidism.

1)surgical removal, total thyroidectomy of thyroid carcinoma, subtotal thyroidectomy (hypothyroidism occurs from 25 to 75 of patients in different series);

2)irradiation (hypothyroidism results from external neck irradiation therapy in doses 2000 rads or more such as are used in the treatment of malignant lymphoma and laryngeal carcinoma); I131 therapy for hyperthyroidism (it results in hyperthyroidism in 20 % to 60 % of patients within the first year after therapy and in 1 % to2 % each year there after);

3)during or after therapy with propylthyouracil, methimazole, iodides or betablockers;

4)autoimmune processes (hypothyroidism usually occurring as a sequel to

Hashimoto’s thyroiditis and results in shrunken fibroid thyroid gland with a little or no function and infiltrative diseases (tuberculosis, actynomycosis);

5)trauma;

6)iodine deficiency.

2.Secondary and tertiary hypothyroidism

It occurs due to either deficient secretion of TSH from the pituitary or lack of secretion of TRH from the hypothalamus.

-Tumor;

-Infarction;

-Infiltrative process;

-Trauma;

-Drugs (reserpin, parlodel).

3.Peripheral hypothyroidism:

-peripheral tissue resistance to thyroid hormones;

-decreasing of T4 peripheral transformation into T3 (in liver or in kidneys) ;

-production of antibodies to thyroid hormones.

Congenital:

-Maldevelopment –hypoplasia or aplasia;

-Inborn deficiencies of biosynthesis or action of thyroid hormone;

-Atypical localization of thyroid gland;

Classification.

B.1. Laboratory (subclinical) hypothyroidism.

2.Clinical hypothyroidism, which can be divided on stages of severity: mild, moderate, severe.

C.1. Compensation.

2.Subcompensation.

3.Decomposition.

D.1. Without complications.

2.With complications (myopathy, polyneuropathy, encephalopathy, coma).

Clinical features

The major symptoms and signs of hypothyroidism reflect showing of physiologic function. Virtually every organ system can be affected. The onset of symptoms may be rapid or gradual, severity varies considerably and correlates poorly with biochemical changes. Because many manifestations of hypothyroidism are non-specific, the diagnosis is particularly likely to be overlooked in patients with other chronic illnesses and elderly.

Nervous system

Most of hypothyroid patients complain of fatigue, loss of energy, lethargy, forgetfulness, reduced memory. Their level of physical activity decreases, and they may speak and move slowly. Mental activity declines and there is inattentiveness, decreased intellectual function, and sometimes may be depression.

Neurological symptoms include also hearing loss, parasthesias, objective neuropathy, particularly the carpal tunnel syndrome, ataxia.

Tendon reflex shows slowed or hung-up relaxation.

Skin and hair.

Hypothyroidism results in dry, thick and silk skin, which is often cool and pale. Glycosoamynoglicanes, mainly hyaluronic acid accumulate in skin and subcutaneous tissues retaining sodium and water. So, there is nonpitting edema of the hands, feet and periorbital regions (myxedema). Pitting edema also may be present. The faces are puffy and features are coarse. Skin may be orange due to accumulation of carotene. Hair may become course and brittle, hair growth slows and hair loss may occur. Lateral eyebrows thin out and body hair is scanty.

Cardiovascular system.

There may be bradycardia, reduced cardiac output, quiet heart sounds, a flabby myocardium, pericardial effusion, cardiac wall is thick, it is increased by interstitial edema. (These findings, along with peripheral edema, may simulate congestive heart failure). Increased peripheral resistance may result in hypertension. The ECG may show low voltage and/or non-specific ST segment and T wave changes. Hypercholesterolaemia is common. Whether or not these

is an increased prevalence of ischemic heart disease is controversial. Angina symptoms, when present, characteristically occur less often after the onset of hypothyroidism, probably because of decreased activity.

Gastrointestinal system.

Hypothyroidism does not cause obesity, but modest weight gain from fluid retention and fat deposition often occurs. Gastrointestinal motility is decreased loading to constipation and abdominal distension. Abdominal distension may be caused by ascities as well. Ascitic fluid, like other serous effusions in myxedema, has high protein content. Achlorhydria occurs, often associated with pernicious anemia.

Renal system.

Reduced excretion of a water load may be associated with hyponatriemia. Renal blood flow and glomerular filtration rate are reduced, but serum creatinine is normal. May be mild proteinuria and infections of urinary tract.

Respiratory system.

Dyspnea of effort is common. This complaint may be caused by enlargement of the tongue and larynx, causing upper airway obstruction, or by respiratory muscle weakness, interstitial edema of the lungs, and for plural effusions which have high protein content. Hoarseness from vocal curt enlargement often occurs.

Musculoskeletal system.

Muscle and joint aches, pains and stiffness are common. Objective myopathy and joint swelling or effusions are less often present. The relaxation phase of the tendon reflexes is prolonged. Serum creatine phosphokinase and alanine aminotransferase activities are often increased, probably as much to slowed enzyme degradation as to increased release from muscle.

Hemopoetic system.

Anemia, usually normocytic, caused by decreased red blood cell production, may occur. It is probably from decreased need of peripheral oxygen delivery rather than hematopoetic defect. Megaloblastic anemia suggests coexistent pernicious anemia. Most patients have no evidence iron, folic acid or cyancobalamin deficiency.

Endocrine system.

There may be menorrhagia (from anovulatory cycles), secondary amenorrhea, infertility and rarely galactorrhea. Hyperprolactinemia occurs because of the absence of the inhibitory effect of thyroid hormone on prolactine secretion (and causes galactorrhea and amenorrhea or Van – Vik – Cheness – Ross’s syndrome).

Pituitary-adrenal function is usually normal. Pituitary enlargement from hyperplasia of the thyrotropes occurs rarely in patients with primary hypothyroidism –such enlargement also may be caused by a primary pituitary tumor, which resulting TSH deficiency.

Enlargement of thyroid gland in young children with hypothyroidism suggests a biosynthetic defect. Hypothyroidism in adults is caused by Hashimoto thyroiditis.

Secretion of growth hormone is deficient because thyroid hormone is necessary for synthesis of growth hormone. Growth and development of children are retarded. Epiphyses remain open.

Metabolic system.

Hypothermia is common. Hyperlipidemia with increase of serum cholesterol and trigliceride occurs because of reduced lipoprotein lipase activity.

Subclinical (laboratory) hypothyroidism.

It is a state in which we cant find clinical features of hypothyroidism and euthyroidism is reached by compensatory increasing of TSH secretion and that’s why synthesis and secretion of such level of thyroid hormone that will be enough for organism. It is an asymptomatic state in which serum T4 and free T4 are normal, but serum TSH is elevated. The therapy may provide the patient with more energy, a feeling of well being, desirable weight reduction, improved bowel function or other signs of better health even though the patient is not aware of these symptoms before therapy.

Diagnostic of hypothyroidism is based on:

1)history;

2)clinical features;

3)blood analysis: anemia; hypercholesterolemia;

4)levels of thyroid hormone: both serum T4 and T3 are decreased (but in 25% of patients with primary hypothyroidism may be normal circulating levels of T3);

5)ECG;

6)examination of tendon reflexes;

7)ultrasonic examination;

Differential diagnosis of primary and secondary hypothyroidism:

1) clinical features:

Secondary hypothyroidism is not common, but it often involves other endocrine organs affected by the hypothalamic – pituitary axis. The clue to secondary hypothyroidism is a history of amenorrhea rather than menorrhagia in a woman with known hypothyroidism.

In secondary hypothyroidism, the skin and hair are dry but not as coarse; skin depigmentation is often noted; macroglossia is not prominent; breasts are atrophic; the heart is small without accumulation of the serous effusions in the pericardial sac; blood pressure is low, and hypoglycemia is often found because of concomitant adrenal insufficiency or growth hormone deficiency.

2) laboratory evaluation:

shows a low level of circulating TSH in secondary hypothyroidism, whereas in primary hypothyroidism there is no feedback inhibition of the intact pituitary and serum levels of TSH are very high. The serum TSH is the most simple and sensitive test for the diagnosis of pituitary hypothyroidism.

Serum cholesterol is generally low in secondary hypothyroidism, but high in pituitary hypothyroidism.

Other pituitary hormones and their corresponding target tissue hormones may be low in secondary hypothyroidism.

The TSH test is useful in distinguishing between secondary and tertiary hypothyroidism in the former; TSH is not released in response to TRH; whereas in the later, TSH is released.

Treatment of hypothyroidism.

1. Diet №10.

2.Regimen is not restricted.

3.1) replacement therapy:

-desiccated animal thyroid (this is an extract of pig and cattle thyroid glands, which standardized based on its iodine content but they are too variable in potency to be reliable and should be avoided);

-synthetic preparations of :

T4 (l-thyroxine)

-T4 is preparation of choice, because it produces stable serum levels of both T4 and T3.

-Absorption is fairly constant 90 to 95% of the dose. T3 is generated from T4 by the liver.

-The initial dosage can be 1.6 mkg/kg of ideal weight or 12.5-25 mkg in older patients and 25-50 mkg in young adult.

-The dosage can be increased in 25-50 mkg increments at 4 to 6 week intervals until clinical and biochemical euthyroidism is achieved. In older patients more gradual increments are indicated. Cautious replacement is particularly warranted in patients with ischemic heart disease, because angina pectoris or cardiac arrhythmia may be precipitated by T4 therapy.

-The average maintenance dosage is 100 to 150 mkg/day orally, only rarely is a larger dosage required. In general, the maintenance dose may decrease in the elderly and may increase in pregnancy.

-The dosage should be minimum that restores TSH levels to normal (though this criterion cannot be used in patients with secondary hypothyroidism).

-Patient takes the whole dose of T4 once a day (in the morning), in the summer the dose may be decreased and in the winter should be increased.

T3 (liothyronine sodium) should not be used alone for long-term replacement because its rapid turnover requires that it be taken. T3 is occasionally used mainly in starting therapy because the rapid excretion is useful in the initial titration of a patient with longstanding hypothyroidism in whom cardiac

arrhythmia may occur early in replacement therapy. The risk of jatrogenic hyperthyroidism is therefore greater in patients receiving these preparations.

In addition, administering standard replacement amounts of T3 (25 to 50 mkg/day) results in rapidly increasing serum T3 levels to between 300 and 1000 mkg within 2 to 4 h, these levels return to normal by 24 h. Therefore, when assessing serum T3 levels in patients on this particular regimen, it is important for the physician to be aware of the time of prior administration of the hormone. Additionally, patients receiving T3 are chemically hyperthyroid for at least several hours a day and thus are exposed to greater cardiac risks. Similar patterns of serum T3 concentrations are seen when mixtures of T3 and T4 are taken orally, although the peak levels of T3 are somewhat lower. Replacement regimes with synthetic preparations of T4 reflect a different pattern of serum T3 response increases in serum T3 occur gradually over weeks, finally reaching a normal value about 8 wk. after starting therapy.

Synthetic T3 and T4 combinations (liotrix, thyreocomb). These preparations were developed before it was appreciated that T4 is converted to T3 outside of the thyroid. These preparations should not be used.

2)Symptomatic therapy:

-beta-blockers (should be used in patients with tachycardia and hypertension) in the dose of 20 – 40 - 60 mg/day;

-hypolypidemic agents;

-vitamins (A, B, E);

-diuretics and others.

Subclinical hypothyroidism

Many endocrinologists would treat such patients with T4, especially if hypercholesterolemia were present. Even in the absence of hyperlipidemia, a trial of therapy might be varianted to determine if the patient experiences improvement presumably the normal serum T4 concentrations before therapy did not reflect adequate tissue effects of thyroid hormones in such patients. Unfortunately, it is also reasonable to follow these patients without T4 therapy by surveying thyroid function at 4-to 6 months intervals to determine whether thyroid failure has occurred, as indicated by the serum T4 falling to subnormal

levels along with a greater increase in serum TSH and the appearance of clear symptoms.

Myxedema coma.

It is a life-threatening complication of hypothyroidism, which is extremely rare in warm climates but not uncommon in cold areas.

Precipitating factors include:

-exposure to cold;

-infection;

-trauma;

-drugs that suppress the CNS.

Myxedema coma characteristics include a background of long-standing hypothyroidism with extreme hypothermia (temperatures 24 to 32), areflexia, seizures, CO2 retention, and respiratory depression caused by decreased cerebral blood flow. Severe hypothermia may be missed unless special low reading thermometers are used. Rapid diagnosis (based on clinical judgement, history, and physical examination) is imperative because early death is likely.

Treatment of myxedema coma.

It is treated with large doses of T4 (250-500 mkg I/v bolus 3 – 4 times a day) or T3 if available (40 – 100 mkg I/v bolus 3 times a day), because TBG must be saturated before any free hormone is available for response. The maintenance dose for T4 is 50 mkg/day I/v and for T3 10 20 mkg/day I/v until the hormone can be given orally.

The patient should not be rewarmed rapidly because of the threat of cardiac arrhythmia.

Hypoxemia is common, so PaO2 should be measured at the outset of treatment. If alveolar ventilation is compromised, immediate mechanical ventilatory assistance is required.

Thyroiditis

The various types of thyroiditis encompass a heterogeneous group of inflammatory disorders of diverse etiologies and clinical features. With all forms of thyroiditis, destruction of the normal architecture of the thyroid

follicular occurs, yet each disorder has distinctive histologic characteristics. For the purposes of understanding the clinical manifestations, thyroiditis is classified according to either the severity or duration of illness using the following scheme:

1.Acute thyroiditis.

2.Subacute thyroiditis:

-subacute granulamatous thyroiditis;

-subacute lymphocytous thyroiditis.

3.Chronic thyroiditis:

-Hashimoto thyroiditis;

-Ridel struma.

4.Specific thyroiditis.

5.Thyroiditis caused by mechanical or physical factors.

Acute thyroiditis

Etiology

Acute thyroiditis it is an acute bacterial inflammation due to a bacterial pathogen, most commonly staphylococcus aureus, streptococcus hemolytica,streptococcus pneumonie, of anaerobic streptococcal organisms. Infection due to other bacterial pathogens, such as salmonella and escherichia coli have been reported, as well as fungal infections such as coccidiodomycosis. Infection occurs either secondary to hematogenous or lymphatic spread, or as a result of direct introduction of an infective agent by trauma. Persistent thyroglossal duct abnormalities have also been associated with acute thyroiditis.

Clinical features

Fever, chills and other systemic signs or symptoms of abscess formation are present. Anterior neck pain and swelling are usual, with pain occasionally radiating to the ear or mandible.

The physical examination suggests the presence of an abscess, with erythema of the skin, marked tenderness to palpation, and at times fluctuance.