Pathology of hypothyroidism

2021-01-27 12:00 AM

Pituitary failure due to benign pituitary adenoma, pituitary surgery, or necrosis of the pituitary gland in Sheehan's disease.

Outline

Hypothyroidism (SG) is a condition that occurs due to a lack of thyroid hormones, causing tissue damage, metabolic disorders. These pathological changes are called hypometabolism.

The disease is quite common, the dominant rate in women, the rate of disease increases with age. The incidence rate is about 1% in women and 0.1% in men, the rate of hypothyroidism is much higher in areas with local goitre.

Reason

Primary hypothyroidism

The disease occurs due to damage to the thyroid gland, accounting for more than 90% of cases of hypothyroidism.

Hashimoto's thyroiditis: This is the most common cause. The thyroid gland can be large or atrophic, sometimes accompanied by Addison and other endocrine disorders.

Complications caused by treatment: Especially with radioactive iodine, thyroid surgery, especially with synthetic antithyroid drugs, less common.

Unreasonable supply of iodine (excess iodine, lack of iodine): Hypothyroidism due to lack of iodine is still a problem in Vietnam.

Subacute thyroiditis, postpartum thyroiditis: usually occurs after the previous stage of thyrotoxicosis, here hypothyroidism is only temporary.

Other causes of primary hypothyroidism:

Lack of an enzyme to synthesize thyroid hormones

Antithyroid substances in food

Lithium: treatment of mental illness.

Secondary hypothyroidism

Pituitary failure due to benign pituitary adenoma, pituitary surgery, or necrosis of the pituitary gland in Sheehan's disease.

Tertiary hypothyroidism. Due to dysfunction of the pituitary in the hypothalamus, rare.

Hypothyroidism due to peripheral thyroid hormone resistance. Uncommon disease.

Pathology

Hypothyroidism - Mucous disease (myxoedema). Common in women, î around the age of 50. The disease often appears slowly, easily confused with the symptoms of menopause.

Clinical

The skin and mucous membranes are infiltrated by a mucus-like substance that contains a lot of water-absorbing polysaccharides, causing non-concave hard oedema.

Mucous skin:

Round face like the moon, expressionless. Many forehead wrinkles look old before age. The eyelids are swollen, clear on the lower lids, the cheeks are slightly purple, with many dilated capillaries, the lips are thick purple, the rest of the facial skin is yellow.

The hands are thick, the fingers are difficult to fold, the skin is cold and sometimes pale, the palms of the feet are yellow (xanthoderma).

Large tongue, low voice (due to vocal cord infiltration), tinnitus, hearing loss (due to Eustache nozzle). When sleeping loud snoring sound (due to nasal mucosa, oropharynx is oedema).

Hard, dry, flaky skin. Dry hair is easy to fall, eyebrows fall, armpit hair, pubic hair fall. Fingernails and legs are brittle and brittle.

Metabolic reduction symptoms:

As a mirror sign of thyrotoxicosis.

Fear of cold, decreased body temperature, cold hands and feet, dryness.

Drink little, urinate less, and excrete urine slowly after drinking.

Weight gain despite poor appetite.

Gastrointestinal: prolonged constipation, accompanied by decreased bowel movements.

Muscle weakness, cramps, muscle pain.

Psychiatric signs and psychoactive vegetative disorders: a state of indifference, lethargy. Impairment of physical, mental, and sexual activities.

Reducing sweating.

Heart:

Slow heart <60l / min, low blood pressure (mainly systolic), the circulation rate reduces these manifestations due to decreased metabolism.

Signs of myocardial infiltration, pericardium.

Pre-heart pain or true angina, shortness of breath during exertion. Heart listening: blurred, slow, sometimes irregular heart sound.

ECG: slow rhythm, low voltage QRS complexes, sometimes ST depression, flat or inverted T waves. The electrocardiogram will return to normal after treatment with thyroid hormones.

X-ray heartbeat big, weak beat. Sometimes effusion of pericardium, fluid has a lot of protein and cholesterol. Echocardiography helps to distinguish pericardial effusion from a mucoid infiltrate in the myocardium. Sometimes blood pressure increases due to atherosclerosis.

Respiratory symptoms:

Shortness of breath, slow frequency, poor respiratory response to hyperco2emia or decreased

O2 blood. Acute respiratory failure is a major symptom of a coma.

Renal function:

Decreased kidney function, decreased glomerular filtration rate, reduced the ability to discharge water when overloaded, so it is easy to lead to water poisoning in hypothyroid patients if water accumulates due to being introduced into the body too much.

Anaemia:

There are at least 4 mechanisms leading to anaemia in patients with hypothyroidism:

Decreased synthesis of hemoglobulin due to thyroxine deficiency.

Iron deficiency due to loss of iron due to menorrhagia, and reduced iron absorption in the intestine.

Lack of malignancy: megaloblastic anaemia with a lack of vitamin B12. Malignant anaemia is often part of an autoimmune disease of chronic thyroiditis combined with parenchymal autoantibodies, diabetes mellitus combined with anti-pancreatic autoantibodies and mating adrenal insufficiency consistent with anti-adrenal autoantibodies (Schmidt's Syndrome)

Endocrine symptoms:

Thyroid: Maybe large, but in most cases, the thyroid is atrophied.

Other endocrine disorders such as menorrhagia, menstrual periods with little or no lactation - lactation, simple lactation.

Frigidity.

Symptoms commonly present in hypothyroidism (According to Perlemuter and Hazard):

Symptoms of decreased metabolism: Fatigue: 99%. Cold fear: 89%. Weight gain: 59%.

Cardiovascular symptoms: Bradycardia: 95%. Thrill: 31%. Pre-heart pain: 25%.

Skin mucosal symptoms: Dry skin: 97%. Reduced sweating: 89%. Tongue large and thick: 82%.

Hair loss: 76%. Pale green: 67%. Hair loss: 57%. Peripheral oedema: 55%. Hoarse voice: 52%. Deaf: 32%.

Gastrointestinal symptoms: Persistent constipation: 23%.

Muscle symptoms: Cramps (cramps)> 70%

Neurological symptoms: Nervousness (Léthargie): 91%. Speak slowly: 91%. Memory loss: 66%. Mental disorders: 35%.

Hypothyroidism coma:

A severe complication of hypothyroidism, rare, usually only found in the cold, occur in hypothyroid patients with inadequate or untreated treatment, with favourable factors such as infection, surgery, trauma, poisoning ... or abrupt discontinuation of thyroxine therapy. The prognosis is usually severe, with mortality more than 50%. Clinically is a silent coma with the following signs:

Lower body temperature, this is a sign of constant, the temperature around 32-350C sometimes lower.

Respiratory disturbances, always present, with episodes of apnoea, decreased alveolar ventilation.

Cardiovascular manifestations such as bradycardia, hypotension, decreased cardiac output, enlarged heart.

In addition to hormone tests to confirm hypothyroidism, in a hypothyroidism coma also showed: Electrolytes blood and urine: There is always a decrease in blood sodium, with a decrease in chlorine, a decrease in blood Protide, causing easy intracellular water retention. leading to cerebral oedema, blood glucose may decrease, ADH increases.

Subclinical

Effect of lack of thyroid hormone on metabolism and peripheral organization:

Basal metabolism decreased less than 10% compared to normal.

The heel tendon reaction time is longer than 320ms.

Blood cholesterol above 3g / l (constant mark). Triglycerides increase in parallel with cholesterol.

CPK (chromium phosphokinase) increased due to high iso - the muscle enzyme of CPK increased 70UI / l.

Isochromatosis or hypochromia, normal or large red blood cells.

Quantification of circulating thyroid hormones:

Total Iode (Iode in hormone) <4 (g / 100ml. T4 <3μg / dl.

FT4I decreased.

T3 < 80mg/dl (< 1,2 mmol/l).

If T3 alone is reduced, it is not enough because T3 can be reduced for reasons other than the thyroid (low T3 syndrome).

FT4 < 0,8(g/dl.(T4 tự do).

Quantitative TSH:

If primary hypothyroidism TSH always increases above 10 (UI / ml (TSH> 20 (TSH> 20 (UI / ml confirm the diagnosis)): indicates primary thyroid damage. necessary if TSH increases clearly).

If hypothyroidism is due to high causes TSH does not increase.

Measure the concentration of radioactive iodine at the thyroid gland:

The concentration of radioactive iodine reaches below 5%, 10% and 20% at the time of 2, 6 and

24h, sometimes even lower (normal: 20%, 30%, 40% at all times above). Thyroid scans show discrete, heterogeneous, and discrete-focused iodine imaging with little benefit in the diagnosis and prognosis of hypothyroidism.

Diagnose

Implementing the quadrants

Not difficult to hunger with typical cases. Hypothyroidism should be considered before all suspected manifestations of an enlarged thyroid or undergoing radioactive iodine therapy or thyroid surgery.

If primary hypothyroidism is suspected: TSH is the best test for a definitive diagnosis. TSH is normal, excludes primary hypothyroidism. Increased TSH (> 20 (U / ml), confirm the diagnosis. If TSH increases slightly (<20 (U / ml)), FT4 should be quantified, if FT4 is low: clinical hypothyroidism, if FT4 is normal: impaired subclinical, in these cases mild hypothyroidism, but increased TSH helps maintain normal T4, clinical symptoms in these cases are unknown.

If secondary hypothyroidism is suspected: Due to suggestive of pituitary damage, TSH usually decreases but sometimes normal, so FT4 should be quantified, and TSH should not be based solely on the diagnosis of secondary hypothyroidism. In these cases, further exploration of the pituitary and hypothalamus should be added.

Differential diagnosis

Old age: Due to physical deterioration, mental and physical sluggish expression, dry skin, hair loss (especially eyebrows), poor cold tolerance, I131 concentration may decrease. The above symptoms may also be partly due to hypothyroidism.

Chronic renal failure: Anorexia, sluggishness, mild oedema, anaemia, differentiated based on increased blood pressure, increased blood urea, blood créatinin ...

Nephrotic syndrome: oedema, anaemia, increased blood cholesterol, differentiated based on the syndrome of fluid and urine.

Langdon Down disease: Intellectual, underdeveloped limbs, short but younger, more active, not dry skin, slanted eyes, white-streaked iris (Brushfield).

Anaemia, malnutrition: pale skin, slight oedema, hair loss may fall but the spirit is not slow, blood cholesterol does not increase, biochemical tests, hormones are required to distinguish.

Obesity: Weight gain, heavy exercise, increased blood cholesterol, but hair does not fall out, normal mind, not afraid of cold, not slow pulse, not slow breathing.

Treatment

Principles of treatment of hypothyroidism

All cases of hypothyroidism require treatment with the exception of hypothyroidism with mild biomarkers such as:

A moderate increase in TSH (<10 (U / ml) .

T3 T4 is normal.

Are at a time when there is no developing disease.

Treatment for hypothyroidism is generally simple and effective: it is primarily based on thyroid hormone replacement therapy.

Except for oedema coma, the treatment of hypothyroidism should not be hasty, it is necessary to confirm a firm diagnosis before performing the treatment.

It is necessary to explain to patients the need for regular and permanent medication administration. In contrast, it is important to understand that there are cases of transient hypothyroidism that do not require long-term treatment.

Treatment should be very cautious in the elderly, heart failure, coronary failure, to accept a partial replacement treatment.

Thyroid Hormone drugs

Extrait thyroid the drug is made from the thyroid gland in animals.

Content: 1cg, 5cg, 10cg (France). 16, 32, 60, 325mg / tablet (US) (Brand name: Amour Thyroid. Thyroteric, Extrait thyroidien choay).

Synthetic thyroid hormone:

Levothyroxine, LT4:

Drug form: V iên compression, lotions, injections. Content; 1 drop = 5μg.

Tablets: 25 - 50 - 75 - 100 - 300 (g. Injections; 200 - 500μg (100μg / ml) (Brand name: Synthroid- levothroid, L Thyroxine - Roche, Levothyrox ...)

Liothyronine, LT3:

Oral form: Tablets.

Content; 5 - 25 - 50 μg. (Brand name: Cynomel).

LT4 combined with LT3:

There are many combinations with different ratios of T4 and T3 (4/1, 5/1, 7/1). The common name in America is Liothrix.

Content: many types, most commonly 100mcg LT4 / 25 mcg LT3 in tablet form also has other contents. (Brand Name: Euthyroid, Thyrolar, Euthyral, Thyreotoin, Thyreocomb)

In treatment, there is also the form of D. Thyroxine. (Dextro - Thyroxine) but the L form Thyroxine is preferred for its stronger effect.

Advantages and disadvantages of drugs:

The half-life of L Thyroxine is about 8 days, explaining a stable drug concentration in the blood, it is only necessary to give orally once a fixed hour of the day. Peripheral deodorized Thyroxine becomes Triiodothyronine (T3).

Particularly for T3 (cynomel) used alone will have much faster effects, but the drug concentration increases dramatically after each oral dose causing discomfort for the patient. The half-life of T3 is 48 hours, the drug needs to be used 2-3 times/day. T3 is generally indicated only temporarily for pre-probe differentiated thyroid Kor radiotherapy.

With Euthyral (a combination of T3 and T4) the drug can also cause a sudden increase in T3 in the blood, so it is also less of a choice in treatment, while extrait thyroiodin is not used in the treatment of hypothyroidism with different ratios of T3 and T4 it is difficult to evaluate the results.

Specific treatment

Thyroxine is the drug of choice at present, the average replacement dose is 75-125 (g / day. In elderly patients, it is often lower, note that the disease requires lifelong treatment.

Start:

If the patient is young and healthy, the dose should be started at 100μg / day. At this dose, hypothyroidism should improve gradually, but it may take several weeks for the T4 to reach constantly. Symptoms decreased after several weeks of treatment. Elderly patients should start with a dose of 50μg / day. Patients with heart disease should have a starting dose of 25μg / day and closely monitor cardiac manifestations during treatment. These patients increased the dosage by 25μg / day per week until the desired therapeutic effect was achieved

Monitor and adjust dosage:

With primary hypothyroidism:

The goal of treatment is to maintain the TSH in the normal range. TSH should be quantified 2-3 months after initiation of treatment. The dose of thyroxine is adjusted from 12-25μg / day every 6-8 weeks until TSH returns to normal. Then just quantify TSH each year to control treatment as desired, should not apply high doses of thyroxine, TSH concentrations below normal levels can cause risk of osteoporosis, atrial fibrillation.

With secondary hypothyroidism:

TSH cannot be relied on to regulate treatment. The goal of treatment is to keep FT4 at normal levels. The thyroxine dose is adjusted every 6-8 weeks until the therapeutic goal is reached. Thereafter, monitoring of FT4 once a year is sufficient to control the disease.

In secondary hypothyroidism (Sheehan's syndrome) often accompanied by adrenal insufficiency, hypogonadism and hypothyroidism, so must accompany with appropriate hormones. The adrenal hormone should be given first to prevent acute adrenal insufficiency when thyroid hormone increases the body's metabolism.

For patients with coronary artery disease:

Thyroxine can aggravate coronary artery disease in particular as well as heart diseases such as heart failure, arrhythmia, need for small doses, very slow dose increase, cardiac status monitoring, electrocardiogram, plus beta-blockers. if necessary (note contraindications). If symptoms of angina persist, even if mild, thyroid hormone therapy should also be discontinued, and intervention for coronary artery therapy may be considered (note to be safe in the context of hypothyroidism).

Difficulties in controlling hypothyroidism

Often due to dissatisfaction with treatment. Some cases need to increase the dose of thyroxine such as:

Drug malabsorption:

Due to intestinal disease or some drugs that interfere with the absorption of drugs such as cholestyramine, sucralfate, aluminium hydroxide, iron sulphate.

Interactions with other drugs:

Increases drug excretion such as rifampin, carbamazepine, phenytoin or inhibition

converts T4 to T3 in the periphery as amiodarone.

Pregnancy:

Thyroxine requirement increased during the first 3 months. In general, it is necessary to increase the dose of thyroxine both for the mother and to avoid large goitre in the baby.

Remaining thyroid function:

Usually deteriorates after hypothyroidism.

Subclinical hypothyroidism:

Thyroxine should be used in the following cases:

Symptoms of hypothyroidism.

There is a large goitre.

Increased blood cholesterol to the point of treatment.

The remaining untreated subclinical hypothyroid patients should be monitored each year, should initiate thyroxine when symptoms of hypothyroidism appear or TSH> 20μg / ml.

Hypothyroidism and surgery

Although hypothyroidism has an increased risk of surgical complications, it is generally not severe. When emergency surgery is required, it can be carried out immediately, but it is necessary to give thyroxine just before surgery, the first dose by intravenous route. Surgery under the program can be delayed until hypothyroidism has been treated for several weeks.

Treatment of coma due to hypothyroidism

Although rare, especially in hot countries, hypothyroidism is an emergency that requires urgent treatment. The treatment regimen includes:

Symptomatic treatment

Respiratory support; oxygen therapy, endotracheal intubation, helping to breathe, and actively treating the dyspepsia. Quickly confirm the diagnosis by quantitative TSH, FT4 before giving thyroxine.

Heat slowly at room temperature of 220C. Overheating can worsen angioplasty and ventricular fibrillation.

Rehydration electrolytes, glucose.

Thyroxine: 50-100μg IV every 6-8 hours for 24 hours, then 75-100μg / day TM until oral. Thereafter, hormone replacement therapy is continued, as usual, once the diagnosis is confirmed. Careful cardiovascular monitoring is required to quickly detect undesirable effects on the heart due to thyroxine.

Hydrocortisone: 100mg intravenously then 50mg intramuscularly every 8 hours during exacerbations, followed by progression can reduce the dose.