Astrid Libman, Julio Libman
Hyperthyroidism is defined as the clinical condition resulting from the exposure and response of the body's tissues to an excess of thyroid hormones.
Hyperthyroid syndrome recognizes multiple etiologies:
- Graves-Basedow disease. It is currently accepted that the fundamental fact in the development of hyperthyroidism of Graves-Basedow disease -symptomatic complex composed of diffuse goiter, thyrotoxicosis, exophthalmia with or without infiltration of periorbital tissues, dermopathy and clubbing- is the alteration of the homeostatic mechanism that adjusts the production of thyroid hormones to the needs of peripheral tissues. In Graves-Basedow disease, the thyroid receptor for thyrotropin (TSH) constitutes the primary autoantigen for the development of this pathology, through the appearance of antibodies directed against it. These anti-TSH receptor antibodies bind to the TSH receptor, activate adenylate cyclase and induce thyroid growth, increased vascularity and the production and secretion of thyroid hormones. The synthesis of stimulating antibodies to the TSH receptor is not inhibited by thyroid hormones, as is the case with pituitary TSH. As a consequence of excess T4 and T3, the pituitary gland reacts normally by inhibiting the production of TSH, which does not respond with an increase in its levels to endogenous or exogenous thyrotropin-releasing hormone (TRH).
- Hyperfunctioning thyroid adenoma (Plummer's disease). It produces thyroid hormones, sometimes only T3, autonomously and independently of the pituitary TSH, which it inhibits. This circumstance determines the lack of functioning of the rest of the thyroid parenchyma, which continues to be dependent on TSH. Most of the hyperfunctioning autonomic adenomas that inhibit TSH fail to produce a sufficient quantity of hormones to induce clinical hyperthyroidism, a circumstance that occurs more frequently when their size exceeds 3 cm. Activating mutations of the TSH receptor have been found in most of these adenomas.
- TSH-producing pituitary adenoma. It is outstanding.
- Trophoblastic tumors, producing a hormone similar to TSH and large amounts of chorionic gonadotropin that have a weak intrinsic TSH activity.
- Multinodular goiter.
- Subacute thyroiditis and chronic thyroiditis with episodes of transient thyrotoxicosis. In both circumstances there is no true hyperfunction, but a transient hyperthyroidism may occur due to the release of preformed thyroid hormone due to the inflammatory process that affects the gland, viral in the first case and autoimmune in the last.
- Exogenous administration of thyroid hormones.
- Thyroid hormone-producing ovarian teratoma.
- Functional metastasis of follicular thyroid carcinoma.
Of the causes mentioned, the most common are Graves-Basedow disease, functioning thyroid adenoma, and exogenous thyroid hormone administration.
T4 (thyroxine) and T3 (triiodothyronine) are general metabolic stimulants. Due to its effect on the tissues, the energetic substrates are used more quickly, the oxidative metabolism is accelerated and the circulatory speed increases simultaneously. The excess of thyroid hormone produces an excessive consumption of calories, a decrease in muscle work per unit of O2 consumption and an exaggerated response to catecholamines. Even when the use of O2 and of the substrates of oxidative metabolism is higher than normal, as is the production of energy and caloric expenditure, the mechanisms to carry out muscle work are less efficient than in normal conditions and the final product of energy use tends to be hot and to a lesser extent effective work.
However, with the increase in heat production, the hypothalamic temperature regulating center acts normally, which makes it stay within the physiological limits when the compensatory mechanisms of heat loss are activated.
There is no single accepted mechanism to explain the actions of thyroid hormone from a biochemical point of view. In any case, it induces an increase in the number of adrenergic receptors, activates ATPase and accelerates oxidative uncoupling.
Symptoms and signs
The clinical manifestations common to all clinical forms of hyperthyroidism constitute a picture that varies with the intensity of thyrotoxicosis, the age of the patient and the presence of diseases in other organs, for example, the heart.
The patient presents with nervousness, emotional instability, anxiety, and insomnia. There is weight loss despite concomitant polyphagia. Heat intolerance and good cold tolerance are evidenced by the need to wear very little clothing in the dead of winter. Asthenia and muscle atrophy are expressions of proximal myopathy due to increased protein catabolism, which translates into difficulty climbing stairs, and which also affects the temporal muscles and the hands. The skin is thin, moist, and hot due to increased heat loss through evaporation and convection. Thyroid hormone itself induces peripheral vasodilation.
Nails can separate from the nail bed, and patients find it difficult to keep them clean. There is hyperreflexia and a fine tremor in the tongue and hands.
The pulse is tachycardic and there may be arrhythmias, especially atrial fibrillation in older people. In these, cardiomegaly, frank heart failure, and coronary insufficiency are more likely. The pulse is equally wide, due to the increase in differential pressure, due to an increase in systolic due to the greater minute volume, and a decrease in diastolic pressure due to less peripheral resistance due to vasodilation to lose heat. The heart is hyperkinetic, and a functional systolic ejection murmur at the base can often be heard due to increased circulatory velocity. Cardiac hyperactivity due to increased sensitivity to catecholamines would be due to an increase in adrenergic receptors induced by thyroid hormones, which also directly increase myocardial actin and myosin concentrations, adenyl cyclase activity, and heart contractility and rate. Many patients report dyspnea, possibly as a consequence of a myopathy that affects the muscles of the chest wall, in addition to cardiopulmonary factors.
Ocular manifestations, a product of sympathetic hypertonia, include scant blinking, palpebral retraction, and a fixed or “hard” and bright gaze. The gynecomastia that occurs on occasions would be the result of increased metabolism of testosterone to estradiol.
Manifestations typical of some forms of hyperthyroidism.
Graves-Basedow disease . The components of this picture, which as mentioned in the beginning, are thyrotoxicosis, diffuse hyperfunctioning goiter, ophthalmopathy, dermopathy and clubbing, can appear in variable combination and frequency, the first two manifestations being the most common.
The presence of a diffuse goiter, sometimes asymmetric, of increased consistency and sometimes with a murmur and thrill, due to the great vascularization of the gland, is observed in at least 90% of patients.
The clinical signs associated with the ophthalmopathy of Graves-Basedow disease can be divided into two components: the sympathetic or spastic, which has already been mentioned, and the mechanical or infiltrative. The latter includes ocular protrusion or exophthalmia of variable degree, unilateral or bilateral, and in the latter case it can be of different magnitude in both eyes. There is periorbital edema and chemosis. There may be ophthalmoplegia, a cause of diplopia. The upward and outward gaze is affected first (direction of movement mediated by the superior rectus), and then the upward and inward gaze is affected (mediated by the inferior oblique). The inability to occlude the eyelids during sleep can lead to corneal ulcers. Even when clinically there appears to be no ocular involvement, Methods such as CT and ultrasonography allow edema and enlargement of the orbital tissues to be verified in most cases. Exophthalmometry with the Hyrtel exophthalmometer is a simple way to quantify ocular proptosis.
Normally the distance from the outer edge of the orbit to the frontal plane passing through the anterior pole of the cornea is less than 16 mm.
The pathogenesis of Graves' disease ophthalmopathy is unclear, postulating an autoimmune mechanism.
The dermopathy of this disease is characterized by the appearance of localized myxedema, generally visible in the anterolateral portion of the leg, and frequently bilateral. The typical form consists of a painless plaque thicker than the surrounding skin, purplish-red in color, with a negative or little obvious Godet's sign. Some patients present vitiligo, as an expression of autoimmune pathology. The fingers can take the form of drumsticks. This can accompany skin changes.
Plummer's disease . In this case, a thyroid nodule of generally increased consistency is palpated on the neck.
Subacute thyroiditis . It gives rise to a temporary hyperthyroidism picture. It is produced by viruses that reversibly destroy the cells that form the follicle wall, determining the release of preformed thyroid hormone. The existence of a spontaneous exquisite pain is characteristic, mainly on palpation, spread to both angles of the jaw and to the ears, as well as odynophagia.
In the presence of a picture suggestive of hyperthyroidism, the diagnosis is confirmed in most cases by uptake of 131I together with the determination of plasma levels of T4 and T3. On few special occasions, it is necessary to resort to other evaluations to certify the diagnosis.
Uptake of 131 I . It measures the avidity of the gland for iodine, in this case 131 I, whose gamma emission is quantified on the anterior face of the neck at 2 and 24 hours after oral administration of a tracer dose.
Normal values range between 5 and 15% and I5 and 25% of the administered 131 I (radioactivity) dose , at 2 and 24 hours, respectively. In Graves-Basedow and Plummer diseases these figures are increased. In subacute thyroiditis, uptake is very low, due to destruction of the follicular cells and due to the inhibition of the pituitary TSH caused by the release of thyroid hormones stored in the follicle. The high uptake of hyperthyroidism has the characteristic of not being suppressed in response to the administration of thyroid hormones, as occurs in normals through the inhibition of TSH by the negative feedback mechanism. In hyperthyroid patients, TSH is inhibited by excess circulating hormone.
Other causes of elevated 131 I uptake include phases of recovery from thyroid suppression following administration of T4 or T3 and subacute thyroiditis, administration of diuretics (due to increased ioduria with increased avidity of the gland), deficiency of I and dyshormonogenesis.
Thyroid scintigraphy . It does not provide a functional diagnosis, but it allows certifying the presence of a hyperfunctioning nodule in relation to the rest of the parenchyma (Plummer's disease).
Determination of total thyroxine (T4t). It comprises free T4 and that bound to plasma transporter proteins (T4 binding globulin, albumin and prealbumin). This last fraction is biologically inactive and constitutes more than 99% of circulating T4. Normal concentrations range from 4.5 to 12 ug%. It is increased in hyperthyroidism and in the initial phases of subacute thyroiditis, as well as in certain conditions in which there is an increase in transporter proteins, where the increase occurs at the expense of T4 linked to them, the individual being euthyroid. Included in this case are genetic causes, hyperestrogenisms as in pregnancy and contraceptive medication, acute intermittent porphyria, and the early phase of acute hepatitis.
Total triiodothyronine dosage (T3t). Plasma levels normally vary between 70 and 220 ng / ml. It is generally increased in circumstances similar to the increase in T4, except in a rare form of hyperthyroidism (called T3 hyperthyroidism) and during the administration of certain medications such as amiodarone to euthyroid individuals, where the peripheral conversion of T4 to T3 is blocked , with elevation of the first and decrease of the last.
Free thyroxine dose (T4l). Normal values range from 0.8 to 2.3 ng / dl. It increases in hyperthyroidism and also during acute febrile illnesses and in treatments with heparin and amiodarone.
TSH dosage . Plasma TSH levels quantified by currently available ultrasensitive methods are undetectable or subnormal. On the other hand, they do not respond to injection of TRH with the increase observed in euthyroid individuals.