Endocrinology and metabolic diseases
Hormones are chemicals produced by specialized glands (e.g., pituitary gland, thyroid gland, pancreas, adrenal glands, etc.) that release them into the bloodstream. Through the blood, hormones also reach tissues or organs distant from the endocrine gland that produces them; the hormones, which could be likened to “keys,” interact with receptors (a kind of “lock”) found in the target organs through a very specific recognition process (of the “key-lock” type); in this way they exert their role, which is to regulate the functions of that organ that has receptors for that particular hormone. In this way, a hormone (“key”) will be able to regulate only that organ with the corresponding receptor (“lock”). However, the same organ may have receptors for more than one hormone, therefore, its function may be regulated by more than one hormone.
The production of hormones occurs through a complex regulatory system. These regulatory systems are, in general, specific to each individual hormone; for example, the synthesis (production) of insulin is regulated by the amount of glucose (sugar) in the blood and that of parathormone (a hormone produced by the parathyroids, small glands located in the neck behind the thyroid) by the amount of calcium. The production of other hormones, such as those produced by the thyroid (Thyroxine), the testes (Testosterone), the ovaries (Estradiol and Progesterone), and the adrenal glands (Cortisol), is regulated by the hypothalamic-pituitary system, through the production of other hypothalamic and pituitary hormones. This highly sophisticated regulatory system is influenced by signals coming from other parts of the body, including the brain (e.g., sleep-wake rhythm) and from the external environment (e.g., stressful events, etc.), which influence, therefore, the release of hormones.
When this regulatory system (hypothalamus-pituitary or peripheral endocrine gland) is altered, major consequences occur that lead to endocrine and metabolic diseases.
Four main types of endocrine diseases can be recognized:
Excessive hormone production results in disorders arising from the uncontrolled stimulation of those functions that, under normal conditions, are regulated by the hormone. In Basedow’s disease (a common form of hyperthyroidism, i.e., increased production of hormones by the thyroid gland, due to the presence of a stimulating antibody), there is an increase in heartbeat, heat production, sweating, appetite, and bowel function, but also in consumption, so that body weight, often, is reduced. In addition, the brain is stimulated and, often, agitation, insomnia, tremors, and anxiety appear;
Reduced hormone production can be the result of “spontaneous” diseases or surgery or medical therapies. The manifestations are the consequence of little hormone and, therefore, the reduction of functions regulated by the missing hormone. For example, hypothyroidism (the lower production of thyroid hormone) is characterized by reduced heart rate, intolerance to cold, lower consumption, reduced metabolism, and often increased body weight. In addition, mood also decreases and depression may appear.
Resistance to hormone action can have a genetic origin (e.g., resistance to the action of thyroid hormones, a very rare syndrome) or it can be acquired (e.g., insulin resistance, a very common syndrome caused by multiple factors, including excess body weight).
Endocrine tumors often do not produce hormones (e.g., non-functioning adenomas of the pituitary gland, or malignant thyroid follicular cell tumors); these neoplasms may be responsible for disorders related to the mechanical effect on neighboring organs or, when malignant, may give localizations in atre locations. However, some tumors may be responsible for clinical manifestations resulting from excessive production of hormones (e.g., Cushing’s syndrome, which is sustained by a pituitary adenoma that produces ACTH and which, in turn, stimulates excessive cortisol production by the adrenal glands; toxic adenoma of the thyroid, a benign, hyperfunctioning tumor of the thyroid, which is responsible for symptoms of hyperthyroidism).
Performance and therapy
The thyroid gland is an endocrine gland, located in the neck, whose function is to produce two hormones (Thyroxine or T4 and Triiodothyronine or T3) that regulate the rate at which all functions of the body occur; T4 and T3 contain four or three atoms of iodine, which is an essential element for the normal activity of thyroid hormones. This element is found in nature in very limited amounts and is taken up, by the body, through the food chain.
About one-third of the world’s population lives in areas where iodine intake through food is insufficient (iodine-deficiency areas). When iodine intake is much less than the daily requirement increased thyroid volume (goiter) is present in most of the population (endemic goiter), and when the daily intake falls further, a congenital defect of thyroid function (congenital hypothyroidism) can occur, which can have serious consequences on the functions of the infant’s brain. The prevalence of endemic goiter in areas with severe iodine deficiency can reach 80% of the population. For this reason, iodoprophylaxis programs have been implemented that have been shown to reduce goiter volume and prevent serious neurological and mental complications in children born in areas of extreme iodine deficiency.
On the contrary, in areas where dietary iodine intake is adequate (iodine-sufficient areas), most people with thyroid disease have autoimmune diseases, ranging from chronic autoimmune thyroiditis (often referred to as Hashimoto’s thyroiditis), which can lead to reduced hormone production (hypothyroidism), to Basedow’s disease, which, on the other hand, can lead to excessive hormone production (hyperthyroidism).
Thyroid tumors usually present as an isolated nodule or in the context of a nodular goiter that sometimes increases in volume. Although thyroid nodules are very common, thyroid cancers are found in a minority of nodules. Thyroid tumors are, however, the most common endocrine tumor and account for about 90% of endocrine gland tumors. Increased thyroid volume (goiter) without nodules (diffuse goiter) is the most common thyroid disease, reaches the highest prevalence before menopause and then decreases with age.
In contrast, the prevalence of thyroid nodules or nodular goiter or anti-thyroid antibodies increases with age. In an epidemiological study, thyroid nodules or nodular goiter were found at ultrasound examination in 33% of people aged 18-65 years. Other studies have found that between 20 and 78 percent of women have at least one nodule detected on thyroid ultrasound.
The pituitary gland is a small endocrine gland located at the base of the brain, behind the root of the nose, in a bony pocket called the sella turcica. The pituitary gland regulates the secretion of hormones from other “peripheral” endocrine glands, which include the thyroid, adrenal glands, testes, and ovaries, by means of specific hormones that are thyrotrophic hormone (TSH), adrenocorticotropic hormone (ACTH), and gonadotropins (FSH and LH), respectively. It also produces growth hormone (GH) and prolactin. The pituitary gland releases into the bloodstream these hormones that have an action at the level of organs and glands distributed throughout the body; these peripheral endocrine glands in turn produce other hormones that through the blood exert a feedback signal on the pituitary gland (feed-back mechanism). Once they come in contact with the hypothalamus and pituitary gland, these “peripheral” hormones provide a signal by which the pituitary gland increases or decreases its production of hormones, depending on the body’s needs. The pituitary gland is connected to the hypothalamus (a part of the brain) through the pituitary pedicle, and it is through the pedicle that the brain regulates the function of the pituitary gland.
Most people have four parathyroids, small glands located in the neck behind the thyroid gland; rarely, there are people who have one or two additional parathyroids, sometimes elsewhere in the neck or chest.
These glands produce a hormone, parathormone or PTH, which plays an important role in maintaining normal calcium levels in the body.
When blood calcium levels are reduced, the response of the parathyroids is to increase PTH production with the goal of bringing calcemia back within normal limits; the kidneys, bone tissue and intestines also participate in maintaining normal blood calcium levels. Under normal conditions, when blood calcium rises, the parathyroids release less PTH, which causes the kidney to retain less calcium; thus calcium in the body is kept constantly within very tight limits.
Normal blood calcium levels are important for proper muscle contraction, bone metabolism, coagulation, and molecular signaling within cells.
The main diseases of the parathyroids are hyperparathyroidism (excessive production from parathormone resulting in increased blood calcium) or hypoparathyroidism (parathormone defect resulting in reduced blood calcium).
The adrenal glands are small endocrine (hormone-producing) glands located in the abdomen, above the kidneys; they have an outer part called the cortical that produces hormones through a series of steps starting with cholesterol (mainly cortisol, and aldosterone and, to a lesser extent, hormones that have a weak action similar to that of sex hormones) and an internal part, called the medullary, which produces adrenaline and noradrenaline, modified amino acids that are produced in response to stress, changing blood pressure, heart rate, and increasing blood sugar.
The adrenal cortical plays a vital function in the body: cortisol regulates general metabolism by mobilizing nutrients, regulates the body’s response to inflammation, stimulates the liver to produce sugar, and participates in controlling the amount of water in the body; aldosterone modifies salt and water levels, thus regulating blood volume and pressure.
The main diseases of the adrenal glands responsible for increased hormone production are hypercortisolism, pheochromocytoma, and hyperaldosteronism; however, the most commonly encountered adrenal pathology is the so-called “incidentaloma”; this is, in most cases, an adenoma (i.e., a benign tumor) that does not produce hormones.
The most common form of pituitary tumor is the adenoma (a benign tumor); most pituitary adenomas originate from the anterior part of the pituitary gland called the adenohypophysis and are almost always benign, often with a favorable response to treatment. Some tumors respond better to medical therapy while surgical therapy is preferable for others. Rarely, external radiotherapy is needed and even more rarely some forms of chemotherapy.
Pituitary tumors can be distinguished into: 1) functioning, based on the type of hormone they overproduce such as prolactin (PRL), growth hormone (GH), adrenocorticotropic hormone (ACTH), or thyroid hormone (TSH); in some cases the adenoma produces more than one hormone simultaneously. Other adenomas are said to be nonfunctioning because they do not produce excess hormones, but sometimes, because of their size, they can impair normal pituitary function causing reduced hormone production (hypopituitarism); 2) according to size: microadenomas, if on MRI they are less than 10 mm in diameter or macroadenomas if larger in diameter; 3) based on the appearance of the cells on microscopic examination after surgery. About 70% of tumors are functioning, and the most common symptoms they are associated with depend on excessive hormone production.
Certain manifestations such as lack of menstrual flow (amenorrhea), milk production outside the post-pregnancy period (galactorrhea), excessive stature growth or change in appearance (gigantism or acromegaly), Cushing’s syndrome, and manifestations from excessive thyroid hormone production may be a warning sign of a functioning pituitary adenoma. In some patients, manifestations due to excessive hormone production may be accompanied by headache, vision changes, altered sleep and eating habits, and sometimes altered thirst and the amount of urine produced throughout the day (diabetes insipidus).
The manifestations of non-functioning pituitary adenomas are related to the mechanical effect these tumors exert on the healthy pituitary gland (e.g., fatigue and loss of energy, related to hypopituitarism) and neighboring structures (e.g., headache and reduced vision). However, even functioning tumors, when large in size, can result in mechanical effects on the normal pituitary gland and brain structures near the pituitary gland in addition to symptoms related to excessive hormone production.
