- Thyrotoxicosis - what is the cellular mechanism of action of thyroid hormones?
- Thyrotoxicosis - causes
- Thyrotoxicosis - symptoms
- Thyrotoxicosis and the hypermetabolic crisis
- Thyrotoxicosis - treatment
Thyrotoxicosis is a condition in which there is a significant increase in the concentration of the thyroid hormones T3 and T4. It is an urgent situation, as it may lead to the death of the patient, so the correct diagnosis and treatment is a great challenge for the doctor. How are the levels of these hormones increased? What diseases may contribute to the development of thyretoxicosis? How to correctly diagnose a patient and what is the treatment?
Thyrotoxicosisis an excess of thyroid hormones in the body. This term is used when a combination of symptoms occurs due to the excess levels of these hormones in the body. The symptoms of thyrotoxicatosis can be extremely bothersome, and some of them can pose a threat to human he alth. There is no one specific cause of excess thyroid hormone in the blood. It can be caused by a number of abnormalities in the functioning of the body.
Thyrotoxicosis - what is the cellular mechanism of action of thyroid hormones?
In the blood, thyroid hormones circulate associated with thyroid hormone binding proteins and are thus transported to peripheral tissues, such as the liver, kidneys, heart, skeletal muscles, intestines, etc.
The main metabolic activity is T3, therefore when T4 reaches the cell it is converted to T3 with the participation of deiodinase. T3 then penetrates into the nucleus of the cell, where its receptor is located. It comes in two forms (alpha and beta) and, depending on the predominance of the concentration of a given subunit, it induces specific actions in the cell.
T3 binds to the ligand-binding domain of the thyroid receptor, which induces conformational changes in the receptor, including displacement of corepressors, binding of coactivators.
As a result of these changes, transcription and translation are stimulated, i.e. processes related to the production of mRNA and the synthesis of specific proteins, e.g. the synthesis of Na +, K + ATPase which regulates the body's electrolyte balance.
The human body is great at regulating the tissue response to thyroid hormones, e.g. by reducing the number of T3 nuclear receptors during starvation, which allows the body to maintain normal homeostasis.
Thyrotoxicosis - causes
Excess thyroid hormones may appear in patients suffering from overt hyperthyroidism, i.e. a situation inwhose thyroid gland increases the synthesis of its hormones or are produced outside the thyroid, e.g. by the ovarian goiter.
"Poisoning" with thyroid hormones may also result from an overdose of drugs containing these substances by the patient.
There are many disease entities in which there is an uncontrolled release of these hormones, e.g.
- 1 phases of de Quervain's subacute thyroiditis,
- postpartum thyroiditis,
- acute phase of Hashimoto's disease (hashitoxicosis),
- post-amiodrate type 2 hyperthyroidism
The increased amount of these hormones may also be caused by the increased activation of the TSH receptor, which occurs in the presence of anti-TSHR autoantibodies and is the cause of Graves' disease.
It may also result from an excess of TSH or hCG in the course of TSH-producing pituitary adenoma, chorionic epithelioma or gestational thyrotoxicosis.
The source may also be a mutation of the TSH receptor and this is the case with toxic nodular goiter and a single autonomic nodule.
There is also a relationship between increased cell weight or excess iodine substrate and excess thyroid hormone. This is the case with type 1 post-amiodarone hyperthyroidism, iodine-induced hyperthyroidism, or metastatic thyroid cancer.
You should also be aware of an inadvertent overdose of thyroid hormones by the patient, or the possibility of gynecological problems such as goiter, which may be the source of the production of thyroid hormones.
In the practice of a physician, correct differential diagnosis is important, because depending on the etiopathogenesis, the correct treatment regimen is established, for example: type 1 post-amine hyperthyroidism is associated with an increased synthesis of thyroid hormones, while in type 2 post-amine hyperthyroidism an increase thyroid hormone levels are due to the toxic effects of amiodarone, which damage thyroid cells and release hormones.
In the first case, we use thiamazole and sodium perchlorate, while in the second, the treatment of choice is prednisone (a glucocorticosteroid).
Thyrotoxicosis - symptoms
Often a patient who has an increased amount of these compounds in the system presents a characteristic clinical picture, which consists of manifestations from individual systems.
Nervous system symptoms:
- psychomotor agitation
- anxiety
- irritability
- insomnia
- tearfulness
- emotional instability
An interesting fact isthe fact that patients over 60 years of age They “react” to elevated levels of thyroid hormones with apathy, weariness and even depression. People with schizophrenia, paranoia, epilepsy develop or worsen the symptoms of these diseases.
Circulatory symptoms:
- palpitations
- tachycardia
- atrial fibrillation
- systolic hypertension
- extrasystolic arrhythmia
- intra-systolic murmur
- puffiness
- angina worsening
In patients over 50 years of age the excess of T3 and T4 manifests itself most often in the so-called Thyroid-cardiac syndrome consisting of
- arrhythmias - usually atrial fibrillation
- worsening of circulatory failure - shortness of breath, edema
- progression of coronary artery disease
Transient ischemia of the central nervous system may also occur, which indicates obstruction of the artery with thromboembolic material due to atrial fibrillation.
These patients usually do not develop the typical symptoms of hyperthyroidism and this is most likely due to a diminished response of biologically older organs and tissues to excess thyroid hormone with relatively preserved cardiovascular reactivity. This may explain the differences in the clinical picture of patients depending on age.
Digestive symptoms:
- diarrhea
- frequent stools
Digestive symptoms are caused by increased peristalsis of the stomach, intestines, etc. Diarrhea is not a common complaint reported by the patient, but may be the predominant indicator in some patients. This can lead to malabsorption disorders and contribute to other deficits.
Losing weight is common despite paradoxically increased appetite, but compensating for the loss associated with an accelerated metabolism can also cause weight gain.
Skin and appendage symptoms:
- sweating
- facial redness
- feeling hot
- hair loss
- gynecomastia
- excessive pigmentation (does not apply to the cheek mucosa)
- onycholysis
Patients choose cool rooms and lighter clothes because they are less able to withstand high temperatures. In extreme cases, a fever of up to 40 degrees Celsius may occur along with pain in the area of the thyroid gland.
Muscular symptoms:
- muscle weakness
- weight reductionmuscle
- thyrotoxic myopathy
In the course of thyrotoxicosis, there is muscle weakness, often manifested when climbing stairs or lifting up from a squat. When the eye muscles are involved, the eyelids droop and double vision occurs.
Visual symptoms:
Thyrotoxicosis can occur in Graves' disease, for which changes in the organ of vision are characteristic. The characteristic symptoms include:
- Graefe's symptom - as a result of the delayed movement of the eyelids in relation to the movement of the eyeball, the limb of the sclera appears above the iris during the downward movement of the eyeballs
- Kocher symptom - an analogous mechanism as in the case of Graefe's symptom, but occurring when the eyeballs move up
- Mobius symptom - inability to keep the eyeballs converging and their divergence
- Stellwag symptom - rare blinking
- Dalrymple's symptom - as a result of contraction of the levator muscles of the upper eyelids, the eyelids are pulled up, which makes the patient look "terrified"
Thyrotoxicosis and the hypermetabolic crisis
Thyrotoxicosis, which may appear in the course of the above-mentioned diseases, may turn into a hypermetabolic crisis. It most often occurs in patients with undiagnosed or improperly treated hyperthyroidism that has led to thyrotoxicosis, so it is so important that a doctor conducts an appropriate medical history and physical examination.
A medic should always suspect a hypermetabolic crisis in a patient with a sudden breakdown of the general condition and in a patient with symptoms of multi-organ failure. There are so-called prodromal symptoms which include:
- arousal,
- insomnia,
- night hallucinations,
- increased muscle tremors,
- fever,
- nausea
- and vomiting.
A full-blown patient presents:
- fever,
- strong agitation,
- increased sleepiness,
- apathy,
- coma,
- epileptic states may occur,
- tachycardia,
- atrial fibrillation,
- heart failure,
- severe dehydration preceded by a period of increased sweating.
To assess the risk of this condition,criteria according to Burch and Wartofsky .
- Body temperature
| 38-38,5ºC | 5 pts |
| 38,6-39ºC | 10 pts |
| 39,1-39,5ºC | 15 pts |
| 39,6-40ºC | 20 pts |
| 40,1-40,6ºC | 25 pts |
>40,6ºC | 30 pts |
|
- Nervous system symptoms
| absent | 0 pts |
| Mild agitation | 10 pts |
| Delirium, psychosis, increased sleepiness | 20 pts |
| Convulsions, coma | 30 pts |
- Gastrointestinal symptoms
| absent | 0 pts |
| Diarrhea, nausea, vomiting, stomach pain | 10 pts |
| Jaundice of unknown etiology | 20 pts |
- Cardiovascular symptoms
- Heart rate
| <90/min | 0 pts |
| 90-109 / min | 5 pts |
| 110-119 / min | 10 pts |
| 120-129 / min | 15 pts |
| 130-139 / min | 20 pts |
>or equal to 140 / min | 25 pts |
|
- Congestive heart failure
| absent | 0 pts |
| Swelling of lower legs | 5 pts |
| Crackles at the base of the lungs | 10 pts |
| Pulmonary edema | 15 pts |
- Atrial Fibrillation
| absent | 0 pts |
| Present | 10 pts |
- Presence of a predisposing factor
| Absent factor | 0 pts |
| Current factor - (patients with untreated or improperly treated hyperthyroidism) e.g. acute infection, trauma, surgery, childbirth, ketoacidosis, myocardial infarction, stroke, transient ischemic attack, radioiodine therapy, administration of contrast agents |
10 pts |
Interpretation of the result
| Thyroid crisis unlikely | <25 pkt |
| Thyroid crisis threatening (further clinical diagnosis) | 25-44 points |
| Thyroid crisis very likely | >or equal to 45 points |
Thyrotoxicosis - treatment
Hypermetobolytic crisis caused by thyrotoxicosis requires urgent medical intervention. Several are used to stabilize the patient's conditionpreparations.
- Antithyroid drugs - thionamides
THIAMAZOL (1-methyl-2-mercaptoimidazole) is used. It works by inhibiting the synthesis of thyroid hormones by blocking the incorporation of iodine into the tyrosine residue in thyreoblobulin.
It inhibits the conjugation of iodothyrosine, which is a process necessary to produce ready-made thyroid hormones. This drug shows its therapeutic effect after some time because it does not inhibit the secretion of previously produced hormones.
- Lugol's solution, i.e. iodine in potassium iodide
It is used at least one hour after the administration of thyrostatic drug to prevent it from being used by the thyroid gland to synthesize new hormones.
The rapid supply of large amounts of iodine causes a significant reduction in its uptake and hormone synthesis, a phenomenon known as the Wolff-Chaikoff effect.
- Beta-blocker - Propranolol
A drug from the group of non-selective beta receptor blockers. It inhibits the stimulation of b1 and b2 receptors in peripheral tissues, thanks to which we can to some extent block the influence of the sympathetic system on the body, which is strongly stimulated by stimulation with high concentrations of thyroid hormones.
- Antibiotic
If an infection is suspected, promptly administer a broad-spectrum antibiotic (empiric antibiotic therapy) until culture results are obtained, and then apply targeted antibiotic therapy to which the bacterium is susceptible.
- Consider sedative or anticonvulsant medication if required by the clinical situation
- It is also important to administer oxygen, compensate for water and electrolyte disturbances and lower the body temperature (cold compresses, paracetamol). Thromboprophylaxis is required because atrial fibrillation has a high risk of stroke. In the event of treatment failure, we may consider plasmapheresis.
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