There calcitonin is a hormone normally produced by parafollicular cells of the thyroid, also called C cells. Calcitonin is used as a tumor marker as it is altered in the presence of medullary thyroid carcinoma, which is a tumor that originates precisely the C cells of the thyroid.
Calcitonin normal values
Currently, using a third generation assay method, i.e. immunochemiluminescence (ICMA) very sensitive, the normal reference values of calcitonin are:
- Calcitonin less than 5 pg / ml for the female sex
- Calcitonin less than 8.5 pg / ml in the male sex.
What is calcitonin and what it is used for
There calcitonin is a polypeptide substance (ie composed of many peptides, molecules formed by amino acids that have a total weight of less than 5000 Daltons) consisting of 32 amino acids and is produced by the parafollicular cells of the thyroid and by the K cells of the epithelium of the airways.
Calcitonin function and mechanism of action
What is calcitonin used for? What is its function? There calcitonin it has an effect on the metabolism of calcium and phosphorus: its physiological function is to lower the blood calcium concentration, thus counteracting the action of parathyroid hormone (parathyroid hormone, PTH).
The action of calcitonin on the calcium metabolism is expressed in the following ways:
- at the level of the kidneys, where it stimulates the tubule to eliminate calcium (Ca2+) and counteracts the action of vitamin D
- in the intestine, inhibiting the reabsorption of calcium introduced with food
- at the level of osteoclasts, inhibiting their bone resorption action and instead stimulating the deposition of calcium ions in the bones
Its action on the phosphatemia on the other hand, it occurs at the renal level, by inhibiting the reabsorption of phosphates at the level of the renal tubules.
What regulates the production of calcitonin?
How is calcitonin production affected? The concentration of the plasma calcitonin is regulated with a negative feedback mechanism: a low kick inhibits the secretion of the hormone; high levels of calcium in the blood, however, they increase its production.
The secretion of calcitonin is also stimulated by the action of hormones such as gastrin and the pentagastrine. In fact, during a meal, the cells of the mucous membrane of the stomach and duodenum produce gastrin following the stimulus generated by the arrival of food in the gastric lumen. In turn, gastrin stimulates the production of calcitonin, with the aim of preparing the storage in the bones of the calcium introduced with food.
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Why calcitonin is dosed
Calcitonin is dosed in the following cases:
- Diagnosis of hyperplasia of thyroid C cellsParafollicular cell hyperplasia of the thyroid consists of an increase in the number of thyroid C cells, and represents a pre-neoplastic lesion which, at times, can progress to medullary thyroid carcinoma. Calcitonin monitoring should therefore be used in people with RET mutation who are predisposed to developing medullary thyroid cancer, even in the context of multiple endocrine neoplasia (MEN).
- Diagnosis of medullary thyroid carcinoma: it is a mostly sporadic (ie non-hereditary) tumor (80% of cases), characterized by the proliferation of thyroid C cells, which degenerate into calcitonin-producing neoplastic cells. In a 20-25% of cases instead it is a hereditary neoplasm.
- Monitoring after thyroidectomy and / or radiotherapy: After removal of medullary thyroid carcinoma, calcitonin can be used as a marker of tumor recurrence, as well as thyroglobulin for follicular and papillary tumors of the thyroid.
- Screening in family members of people with medullary thyroid cancer and multiple endocrine neoplasia.
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THE high calcitonin values I'm:
- Calcitonin equal to or greater than 5 pg / ml for the female sex
- Calcitonin equal to or greater than 8.5 pg / ml in the male sex.
Causes of high calcitonin
What are the causes of high calcitonin? what does a rise in calcitonin mean? A match by high calcitonin the presence of medullary thyroid carcinoma must always be differential diagnosis. This is correct following the principle that in medicine the most serious pathologies must first be excluded, and then go on to diagnose less important pathologies.
Here are the major causes of high calcitonin, sorted from most to least frequent.
- Medullary thyroid cancer: as already mentioned, in this type of tumor the neoplastic cells are responsible for an overproduction of calcitonin. Only in 20-40% of cases of hypercalcitoninemia (elevated calcitonin), medullary thyroid carcinoma is then diagnosed. In other cases, the causes of high calcitonin they must be sought in a series of conditions that can be physiological or pathological. Here are the most frequent causes of high calcitonin.
- Hyperplasia of C cells or thyroid parafollicular cells: it is a condition characterized by the presence of hyperplasia (therefore by a high number of thyroid C cells, with consequent overproduction of calcitonin and the finding of high calcitonin in blood tests. Hyperplasia of thyroid C cells can represent a "pre- neoplastic ”(ie predisposing to the development of medullary thyroid carcinoma), but it can also be a condition unrelated to the tumor and secondary to other situations stimulating the proliferation of non-malignant C cells.
- Using proton pump inhibitor (PPI) drugs: the use of proton pump inhibitor drugs (among the most used we remember omeprazole, lansoparzole, pantoprazole, esomeprazole) can cause an increase in gastrin, in response to a reduction in the secretion of gastric hydrochloric acid, with consequent reduction of the acidity of the stomach. stomach. Hypergastrinemia can in turn cause a increased production of calcitonin, even after only 4-8 weeks from the start of treatment.
- Hypergastrinemia: the presence of elevated gastrin in the blood determines the stimulation of thyroid C cells for a greater production and secretion of calcitonin. Hypergastrinemia, in addition to the use of proton pump inhibitors as explained in the previous point, can be caused by a gastrin-producing tumor (gastrinoma) or in the presence of chronic atrophic gastritis, a pathology characterized by the attack on the gastric parietal cells by of abnormal auto antibodies, resulting in hypochlorhydria (reduced gastric acidity), pernicious anemia and gastrin hypersecretion, to try to correct the reduced gastric acidity. These are all situations that therefore lead to the finding of high calcitonin. On this principle is based the pentagastrine test: which consists in the rapid infusion of pentagastrin (0.5 µg / kg, ie 0.5 µg per kg of body weight), with measurement of basal calcitoninemia (at time 0), and then at 2, 5 and 7 minutes. A peak elevation, between 2 and 5 minutes greater than 100 pg / ml or in any case 3-5 times the initial value, is indicative of a neoplastic form. On the other hand, concentrations below 30 pg / ml or a flat concentration growth curve can lead to the exclusion of thyroid neoplastic cells. The most common side effects of the pentagastrin stimulus test can be: nausea and vomiting, precordialgia (chest pain), tachycardia (high heart rate), metallic taste in the mouth, abdominal cramps and esophageal spasm
- Kidney failure: Reduced renal function, which results in decreased creatinine clearance with urea and high creatinine in the blood, can cause "buildup" of reduced elimination calcitonin, with secondary evidence of elevated blood calcitonin levels.
- Hypercalcemia: high circulating calcium levels stimulate thyroid C cells to produce greater quantities of calcitonin, due to the feedback mechanism by which calcitonin tends to lower calcium levels by counteracting the action of vitamin D and parathyroid hormone (PTH). Therefore, all situations causing high calcium in the blood can cause hypercalcitoninemia. On this principle is based the football test (rapid intravenous infusion of 2 mg / kg of weight (i.e. 2 mg of calcium for each kg of our body weight), with calcitonin dosing 5 minutes before the infusion, at minute 0 i.e. at the same time as the infusion of calcium, and then at 2, 5 and 10 minutes). To perform the calcium test you must be fasting and have first performed an electrocardiogram (ECG) that certifies the absence of arrhythmias or predisposing factors to cardiac arrhythmias, and a dosage of renal function (urea, creatinine) and ionmia (Calcium , Magnesium, Phosphorus, Potassium, Sodium) for the purpose of highlighting severe renal failure and possible dysionemias, which contraindicate the examination. Other contraindications to the test are metabolic diseases such as galactosemia and lactase deficiency. The test may cause some side effects such as: nausea, flushing and / or skin redness, low blood pressure (hypotension) or high blood pressure (hypertension), paraesthesia (altered perception of skin sensitivity) in the face or limbs, ageusia ( taste disturbance), bladder tenesmus (urge to urinate, i.e. urge to urinate). Values greater than 100 pg / mL or values increased beyond 300% from baseline are considered indicative of the presence of neoplastic (tumor) cells.
- Thyroid cancers other than medullary thyroid carcinoma: There is evidence in the literature that papillary and follicular thyroid carcinoma can indirectly stimulate the C cells of the thyroid through substances released by them into the bloodstream. It is a very rare occurrence, this type of neoplasms produces in most cases the thyroglobulin, which is a precursor substance for thyroid hormones.
- Hashimoto's thyroiditis: in the course of chronic lymphocytic thyroiditis, hyperplasia of the thyroid C cells has sometimes been observed, with consequent hyperproduction of calcitonia and finding of elevated levels of the latter in the blood. In this context, the dosage of TSH, fT3 and fT4 and the possible presence of antibodies to thyroid peroxidase and anti thyroglobulin.
- Neuroendocrine tumors: neuroendocrine neoplasms are neoplasms that originate from the cells of the neuroendocrine system, present throughout the organism and especially in the pancreas, thyroid, gastrointestinal tract, adrenal glands, lungs, thymus. Some of these tumors may be responsible for an ectopic hyperproduction of calcitonin (the best known are pheochromocytoma, lung microcytoma, paraganglioma, enteropancreatic tumors, insulinoma, VIPoma, gastric carcinoid tumor.
- Age: with the passing of the years the average levels of calcitonin seem to decrease slightly (therefore higher calcitonin in young people than in the elderly).
- Physical activity: exercise has been hypothesized to increase calcitonin levels for the days following exertion.
- Pregnancy: during pregnancy, the body needs calcium concentrations higher than normal, with the risk that the bones are "too depleted" by this increased need for Ca. A higher than normal amount of calcitonin is therefore produced to "safeguard Calcium from the bones and prevent it from being removed in excess.
Drugs that interfere with dosing
In addition to the proton pump inhibitors, which constitute one of the most frequent conditions of non-tumor increase in calcitonin, we list below other drugs that can alter the blood dosage of this hormone:
- glucocorticoids: drugs used as cortisol agonists, among the most used we remember cortisone (Cortone Acetate), prednisone (the famous Deltacortene), prednisolone (Deltacortenesol), methylprednisolone (Solumedrol, Medrol, Urbason), hydrocortisone (Flebocortid, Solucortef), betamethasone (Bentelan), dexamethasone (Decadron, Soldesam).
- glucagon: trade name Glucagen, is a drug indicated for the treatment of severe hypoglycaemia, can raise blood levels of calcitonin
- beta blockers
- CGRP: Calcitonine gene-related peptide receptor antagonist: they are drugs which act against a molecule believed to be responsible for triggering migraines, which is produced by the same gene that produces calcitonin.
High calcitonin symptoms
What are the symptoms of elevated calcitonin? THE symptoms of high calcitonin they are manifold, and none is a specific symptom for an exclusive of hypercalcitoninemia (in other words they are symptoms that can also be found in situations other than the increase in calcitonin).
If the finding of elevated calcitonin is related to the presence of medullary thyroid carcinoma, the symptoms of elevated calcitonin could be:
- Swelling (swelling), including pain and / or the presence of a palpable mass in the front of the neck.
- Sore throat or neck.
- Hoarseness, change in tone of voice.
- Difficulty swallowing (dysphagia) or breathing (dyspnea) in more advanced cases.
If medullary thyroid cancer is framed in the context of a multiple endocrine syndrome type MEN 2, associated with pheochromocytoma and hyperparathyroidism, the presence of hormones produced by these neoplasms (ACTH, VIP (vasoactive intestinal polypeptide, serotonin, prostaglandins, acllycreine) can give rise to a multitude of symptoms. For example, ectopic secretion syndrome of ACTH (sometimes associated with medullary thyroid carcinoma, i symptoms found resemble those of Cushing's syndrome and can be:
- onset of arterial hypertension and / or diabetes mellitus
- streaks of the skin (red stripes on the skin) on the sides
- facies lunaris (poorly expressive face, very swollen, with reddened knobs)
- trunk obesity, called truncular obesity or android obesity, with accumulation of fat in the abdomen
- buffalo hump (accumulation of fat in the upper back, between the shoulders)
- myopathy in the upper and lower limbs
- oligo-amenorrhea (rarefaction of menstruation until the complete interruption of the menstrual cycle)
- loss of libido (sexual desire)
- predisposition to osteoporosis (greater fragility of the bones)
The concept of low calcitonin it is not correct, as there is no calcitonin value to be defined as low. Calcitonin is in fact normal for values between 0pg / ml and 5 pg / ml in women, and between 0 pg / ml and 8.5 pg / ml in men.
Low Calcitonin Causes
The causes of low calcitonin, as already mentioned, it is in fact the conditions of normal body homeostasis, with the absence of hypercalcemia and alterations in calcium metabolism and the absence of tumor and non-tumor conditions that determine an alteration of calcitonin.
Low Calcitonin Symptoms
There are not symptoms of low calcitonin, as there is no defined calcitonin level as low.
Calcitonin how it is measured
Calcitonin is measured by a venous sampling. It is not necessary to be fasting to carry out the sample. The attending physician will be informed of all the medical therapy in progress and of the lifestyle in order to correctly evaluate the calcitonin values found.
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