Acromegaly, symptoms and treatment, symptoms, diagnosis and treatment

The name of this disease is of ancient Greek origin. The root "akros" means limb, and "megas" means big. Acromegaly, known to mankind since antiquity, is characterized by enlargement of the feet and hands and enlargement of facial features. The reasons why this happens are also known: the disease is provoked by a pituitary adenoma that produces excessive secretion of growth hormone, as well as non-pituitary tumors that produce a factor that releases this hormone.

At the Nizhny Novgorod clinic "Alfa Health Center", the disease can be diagnosed during an examination by an endocrinologist. Sometimes, in the presence of characteristic symptoms, it is identified during the comprehensive program “Life without headaches”: pain syndrome with acromegaly is not uncommon.

Causes

This severe neuroendocrine disease is caused by overproduction of somatotropin, or growth hormone. Often the root cause of the pathological process is a benign neoplasm that produces somatotropic hormone in isolation. Regular traumatic brain injuries, chronic sinusitis and a tumor of the hypothalamus can provoke the appearance of a tumor. There are known cases of genetic inheritance of the disease. Often with acromegaly, the tumor increases the production of not only growth hormone, but also prolactin.

The vast majority of known cases of the disease are associated with pituitary adenoma or growth hormone secretion. But data have also been recorded on the development of acromegaly under the influence of ectopic secretion of a hormone that releases growth hormone, which is already responsible for pituitary hyperplasia.

Folk remedies

Acromegaly is caused by a tumor that changes the level of hormones in the body. Folk remedies cannot affect the development, progression and activity of the tumor, so they are not used in practice. Attempts to refuse the help of official medicine and treat pituitary adenoma using traditional recipes can lead to a deterioration in the patient’s condition and the development of serious complications.

The information is for reference only and is not a guide to action. Do not self-medicate. At the first symptoms of the disease, consult a doctor.

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Symptoms

The prevalence of acromegaly in European countries is estimated at approximately one case in 100-250 thousand. According to medical reports, the diagnosis is most often made in patients in the middle age group. Among women and men over 40 years of age, the prevalence of acromegaly is approximately the same. Due to the fact that it develops gradually and progresses slowly, the disease is most often detected 4-10 years after the onset of development.

Active production of growth hormone leads to increased production of somatomedins: these are the names of growth factors, among which the most important role is played by somatomedin C, or insulin growth factor. It is produced in the liver. In addition, acromegaly is accompanied by the production of growth factors of various organs - cartilage, bone and others. Sometimes, if the disease began in adolescence, lengthening of the skeletal bones is possible. This clinical syndrome in acromegaly is called gigantism.

Patients with acromegaly are characterized by a gross change in appearance. They enlarge:

language;
lips;
brow ridges;
nose.

Pathological folding and thickening of the skin is observed. Diastema develops - the gap between the teeth increases. Prognathism is not uncommon - one of the types of facial profiling, which involves the protrusion of the lower jaw forward. The hands and feet increase in size.

With acromegaly, the voice becomes rougher. This occurs due to thickening of the vocal cords. Another reason for voice changes is the expansion of paranasal cavities.

Patients with acromegaly may complain of pain in the spine and joints. They can be caused by the development of arthropathy and their destabilization. In the area of natural folds, hyperpigmentation of the skin and villous-warty growths are observed, and in women, increased growth of body hair according to the male pattern is possible - a syndrome also called hirsutism.

Acromegaly is often accompanied by an enlargement of the thyroid gland and the appearance of nodules. The patient may also develop other diseases of the endocrine system, such as insulin-resistant diabetes mellitus. Cardiovascular pathologies caused by acromegaly - high blood pressure, cardiomegaly, microcardiodystrophy - pose a great danger. The latter is characterized by the fact that it can cause coronary insufficiency and, as a consequence, death.

Damage to the respiratory system in acromegaly is manifested by obstructive sleep apnea. The syndrome is associated with a pathological increase in the size of the epiglottis and tongue. Also, in a patient with acromegaly, the incidence of restrictive pulmonary diseases that are associated with changes in the spine (kyphoscoliosis) increases. There may be decreased sensitivity in the fingers. The symptom is explained by compression of the nerve due to changes in the soft tissues in the wrist area. Acromegaly is also characterized by signs of general malaise - decreased ability to work, causeless weakness and fatigue.

As the tumor grows in size, it puts pressure on healthy pituitary cells. The consequence of this is a disruption of the normal functioning of the organ. In this case, acromegaly is the cause of reproductive and sexual dysfunction, which manifests itself:

menstrual irregularities and female infertility;
decreased potency and libido in men;
various neurological symptoms;
the appearance of headaches, poorly relieved by analgesics, sometimes simultaneously with the appearance of photophobia and lacrimation.

Why does acromegaly develop?

Symptoms characteristic of acromegaly develop as a result of excessive production of growth hormone by a benign tumor (adenoma) of the anterior pituitary gland; a synonym for growth hormone is somatotropic hormone, therefore an adenoma that produces this hormone is also called somatotropinoma.

Most often, when acromegaly is detected, people ask questions about the reasons for the development of adenoma in them (“Why me?” and “What caused the growth of the adenoma?”).

For most people asking, the answer will be: “It’s not known exactly.” The thing is that there are assumptions about the connection between the growth of pituitary adenomas and head injuries, receiving high doses of radiation, but most people did not have these factors in their lives, and acromegaly developed.

A pituitary adenoma develops if 1-2 cells that already secrete GH (somatotrophs) decide that they will no longer obey regulation, but will secrete more GH than necessary and, in addition, divide. As a result, a tumor grows and produces growth hormone. These processes are caused in the vast majority of cases by sporadic, that is, random, mutations in specific cells. There are so many variants of mutations that it is currently impossible to diagnose them, and even if it is possible, it is not always possible to associate mutations with the development of acromegaly.

Complications

Acromegaly, as it progresses, can cause high blood pressure and the development of arterial hypertension. Complications of the disease in the form of cardiomyopathy (an increase in the size of the heart muscle) and other disorders of the cardiovascular system are common. Patients with acromegaly often have diabetes mellitus, osteoarthritis, and thyroid pathologies.

Other possible complications include:

colon polyps;
loss or deterioration of vision;
spinal cord compression;
hypopituitarism - decreased secretion of pituitary hormones.

Patients with acromegaly often develop sleep apnea, a condition in which breathing stops for short periods during sleep. For women, the risk of developing a benign uterine tumor - fibroids - increases. When acromegaly is treated early, the severity or likelihood of all of these complications decreasing.

What happens if acromegaly is not treated?

Acromegaly is a slowly progressive disease. It causes complications that can be independent diseases and themselves cause complications, for example, diabetes mellitus, hypercholesterolemia, arterial hypertension, etc. A detailed list and diagnosis of complications can be found here. As a rule, the main thing that worries you over a long period of time is arthropathy (joint damage), which begins with limited joint mobility, then slowly progresses, causing pain, and then destruction of the joint, often with deformation and even greater pain. When a joint is destroyed, an effective treatment method is joint replacement. Diabetes mellitus usually does not cause pain or bother, but at the same time it is an equally formidable complication and, if diagnosed too late, it will also cause all its inherent complications in addition to the complications of acromegaly. Therefore, to prevent complications, it is necessary to carry out early diagnosis, and treatment should be as effective as possible and carried out as soon as possible.

Danger of disease

If acromegaly is not treated promptly, it can lead to severe complications and death. Approximately half of patients die before the age of 50 years. Moreover, the overwhelming number of deaths with acromegaly (60%) are associated with cardiovascular complications. Another quarter consists of pulmonary-respiratory complications and 15% - the development of oncological processes, most often of the digestive system.

The danger of acromegaly is that it often goes unrecognized. The rarity of this disease, as well as the gradual development of changes in appearance over a long period, do not cause suspicion in the patient. Delayed diagnosis and treatment of acromegaly increases the risk of complications. With timely consultation with a doctor, on the contrary, it is possible to significantly reduce the external manifestations of pathology and side effects.

Forecast

Acromegaly in the absence of therapy is characterized by a progressive course with the development of organ disorders, early disability and premature death (mortality compared to the general population indicator is 2-2.5 times higher; without treatment, patients die 10 years earlier than healthy people). The younger the patient is at the time of the onset of the disease, the more aggressive growth the tumor is characterized by and the higher its functional activity. When it debuts at the age of over 50 years, the tumor grows more slowly and has less hormone-producing activity.

Stages

There are 4 stages of acromegaly:

preacromegaly;
hypertrophic;
tumor;
cachectic.

The first stage is diagnosed extremely rarely due to the mild severity of the symptoms characteristic of acromegaly.

At the hypertrophic stage, acromegaly can be recognized by the enlargement of individual organs, changes in facial contours and protrusion of the lower jaw. Characteristic features at this stage include deepening of the voice, increased body weight, and visual impairment. There are frequent cases of increased sweating due to the fact that the sweat glands also increase in size. General weakness and headaches are also included in the clinical picture of hypertrophic acromegaly.

At the tumor stage, the patient develops increased intracranial pressure. The consequence of this may be severe headaches, decreased hearing and vision. The tumor stage of acromegaly is often accompanied by muscle atrophy and weakness.

The outcome of the disease is considered to be the cachectic stage. This is complete exhaustion that develops in the absence of therapy.

Medicines

Photo: yachist.ru

Drug therapy is carried out using somatostatin analogues and dopamine receptor agonists. Somatostatin analogues are first-line drugs. Suppress the production of growth hormone. In more than half of the cases, they ensure a decrease in hormone levels to normal. In a number of patients, they help reduce the tumor by 10-50 percent or more. Available in the form of short-acting and long-acting products.

Possible side effects are stool disturbances, formation of gallstones, decreased heart rate, hair loss and carbohydrate metabolism disorders. As a rule, the negative consequences of taking it are minor or moderate and do not imply discontinuation of the medication. The effectiveness of therapy should be assessed 3 months or more (optimally six months) after the start of treatment.

Dopamine agonists are prescribed with a moderate increase in the concentration of insulin-like growth factor, more often in combination with somatostatin analogues. Medicines can cause headaches, orthostatic hypotension, gastrointestinal disturbances, and nasal congestion.

Diagnostics

To diagnose acromegaly, the patient is prescribed an oral glucose tolerance test. The diagnosis is confirmed by a biochemically increased concentration of growth hormone in the blood serum. When diagnosing acromegaly, the doctor also takes into account the level of insulin-like growth factor.

Imaging studies are usually sufficient to assess the size and extent of tumor spread. The clinical consequences of acromegaly are determined through echocardiography and analysis of sleep apnea attacks.

Severity of acromegaly

Mild - tolerance to normal physical activity remains, but there may be restrictions in performing heavy physical activity. Hospitalization is not required;
Average - maintaining the ability to self-service, the inability to perform any work. Activity - 50% of waking time;
Severe - restrictions on self-care and any other activities. The patient remains in bed or sits (inactive) more than 50% of the time he is awake.

Treatment

Treatment for acromegaly includes surgery, radiation therapy, and drug suppression of growth hormone secretion.

Ablative therapy is indicated in most cases. The approach varies depending on the individual patient, but transsphenoidal resection is most often used due to its minimal morbidity. It is prescribed if the level of pituitary hormones, which is fixed after a glucose load, reaches normal values.

Irradiation of the tumor is carried out with ultra-high voltage current. In some cases, radiation therapy and surgery are combined.

Drug therapy is carried out if surgery and radiation therapy are contraindicated. The doctor prescribes medications that effectively suppress the secretion of growth hormone. The most commonly used are somatostatin analogues or bromocriptine mesylate.

The vast majority of patients show improvement after a course of therapy. Acromegaly can be brought under control, as a result of which the patient’s life expectancy reaches the population average. However, even with a high level of hormonal control and timely treatment, some negative consequences of the disease, including changes in quality of life and regular joint pain, remain.

How to treat acromegaly?

Due to the fact that this disease is caused by an adenoma and this is the whole reason, it is logical that it needs to be removed. For some reason, it is with tumors of the pituitary gland that patients are always most afraid of surgical treatment. Therefore, I will answer a few frequently asked questions.

Will they go into my brain to remove the adenoma?

No! Currently, the vast majority of operations are performed transnasally and access is made directly to the pituitary gland without affecting any other brain structures. Access scheme:

As you can see, the pituitary gland is located in such a way that transnasal (through the nose) access is very convenient, and at the end of the operation, everything that was opened is closed back and sutured or glued (depending on the type of tissue and structural features and location)

Will I have a craniotomy?

This is not necessary for transnasal access. Currently, transcranial access is used extremely rarely and only in extremely severe cases, when it comes to either survival or disability if surgical treatment is not performed.

Is there a chance that the adenoma will grow again?

Unfortunately, there is such a chance and it increases in proportion to the size of the adenoma. Thus, relapse after removal of a microadenoma (adenoma less than 1 cm in diameter) is approximately 20%, and for a macroadenoma (more than 1 cm) 70-100%, depending on growth characteristics.

If the tumor can grow back, then why operate?

The fact is that somatotropinomas are one of the most aggressively growing hormonally active tumors of the pituitary gland and in order to achieve positive results in treatment, including to prevent complications, it is necessary to treat surgically. This does not mean that surgical treatment should be immediately recommended to everyone indiscriminately as soon as possible, because sometimes with proper preparation of the patient for surgical treatment, the likelihood of relapse (reappearance of adenoma) can be significantly reduced.

How can you reduce the risk of tumor recurrence after surgery?

Each somatotropinoma, despite the same name, is unique. In order to identify all the features, it is necessary to evaluate several parameters by which adenomas are divided:

1. According to the size of the adenoma:

Microadenoma less than 1 cm
Macroadenoma more than 1 cm
Giant adenoma more than 4 cm

The size itself means practically nothing, but as a rule, the larger the adenoma, the more difficult it is to radically remove it, which is not directly related to the size, but to

2. In the direction of growth:

Intrasellar. That is, the adenoma does not extend beyond the sella turcica (the bone structure in which the pituitary gland is located)
Suprasellar growth. Growth upward, to where the optic chiasm is located and if it is compressed, a violation of the peripheral visual fields will develop, in rare cases, blindness
Laterosellar growth. Growth to the sides, to where the internal carotid arteries are located. If the adenoma grows to them, it can grow into the tissue surrounding the arteries and it will be almost impossible to completely remove it. At the same time, the adenoma, as a rule, does not pose a threat to the arteries themselves, since it does not compress them, but clasps them (overgrows them).
Infra and antesellar. Growth forward and downward, to where the nasal cavity is. Often, upon examination, otolaryngologists can detect such an adenoma in the nose.
Retrosellar. Growing backwards, where the medulla oblongata is located. This growth option is quite rare, but if the adenoma grows towards the medulla oblongata, then it is a potential threat to life; it contains the centers for regulating the most important functions of the body, such as breathing and heartbeat.

3. Sensitivity to treatment with somatostatin analogues:

Low: decrease in IGF-1 during trial treatment with Octreotide less than 30%
Moderate: decrease in IGF-1 during trial treatment with Octreotide 30-60%
High: decrease in IGF-1 during trial treatment with Octreotide more than 60%

Methods for determining sensitivity are known and used in the following clinics

Thus, it is clear that there can be many variants of adenoma.

I will outline 3 simple options:

1. Microadenoma with intrasellar growth and high sensitivity to Octreotide is the most favorable for treatment. During surgical treatment, there is a great chance of complete recovery; preoperative preparation does not play a special role, since it does not affect the results of the operation. Immediately before surgery, it is advisable to use Octreotide to relieve swelling and facilitate anesthesia.

2. Macroadenoma with laterosellar growth (with ingrowth into the cavernous sinuses) and high sensitivity to Octreotide is an intermediate option. In this case, it is better to treat with long-acting somatostatin analogues for 6-12 months to reduce the size of the tumor and increase the chances of radical removal (complete cure).

3. Macroadenoma with suprasellar growth (with compression of the optic chiasm) and low sensitivity to Octreotide. Such an adenoma is subject to prompt surgical treatment; one should not expect a decrease in the volume of the adenoma during treatment with somatostatin analogues; most likely, it will grow despite drug treatment.

Choosing the right tactics, taking into account all the details, is the task of a specialist; I just gave you simple options as an illustration.

Is surgery unavoidable?

If you are recommended for surgical treatment and you want to live long and well, then do not refuse, this is the only way to be cured once and for all.

Which neurosurgeon should I contact?

A neurosurgeon must regularly operate on tumors in the pituitary gland region. If he carries out at least 50 such operations in a year, then it is worth contacting him, since by European standards he is a highly qualified specialist.

I was operated on, what next?

At the hospital, you have already had a blood test done for growth hormone. Then after 3 months you can take a blood test for IGF-1 and GH, the target values of IGF-1 are within the reference values, and GH is less than 1 ng/ml. Also, starting from 3 months, an MRI of the pituitary gland can be performed to assess the presence of residual tumor tissue.

What if GH and/or IGF-1 remains elevated after surgery?

In this case, it is necessary to use the next line of treatment, this is drug therapy. The most effective drugs for acromegaly are somatostatin analogues (Octreotide and Lantreotide); if the effectiveness is insufficient, therapy with dopamine agonists can be increased; from this group, the only drug recommended for the treatment of acromegaly is Cabergoline.

Are there any side effects from somatostatin analogues?

They are. The most common are nausea, vomiting and diarrhea. These symptoms may appear and continue throughout the period of action of the drug, therefore, before using long-acting forms of somatostatin analogues, it is necessary to conduct a trial treatment with drugs with a short-term effect.

In addition to quickly developing side effects, there are also delayed ones. Somatostatin analogues are known to promote the development of cholelithiasis (GSD). But it is worth remembering that in people without any gallbladder diseases this effect should not be expected, since it develops almost exclusively against the background of existing problems; somatostatin analogs can only accelerate the course of existing diseases, but not cause them. In addition, to prevent the development of cholelithiasis in people predisposed to this, it is possible to recommend taking ursodeoxycholic acid (UDCA) drugs.

What are the side effects of Cabergoline?

Cabergoline causes a decrease in blood pressure and increased salivation, so it is advisable to take it before bed and start with small doses, gradually increasing (only under the supervision of a doctor!). Also, while taking Cabergoline, it is necessary to perform a cardiac ultrasound at the beginning of therapy and then annually.

Persons with acromegaly

Among famous, public people there are quite a few carriers of the disease acromegaly. Despite this, they are successful, work, and do what they love.

A clear example of acromegaly is a resident of Turkey, Sultan Kosen. His height is 2.51 cm. The tallest man in the world lived from 1918 to 1940. His height is 2.88 cm

Fyodor Makhnov was born in 1875 in the Russian Empire, his height was 285 cm, he weighed 182 kg, foot length - 51 cm, palm 31 cm. He died at the age of 34, presumably from lung disease.

Basketball players with acromegaly:

Cheno-Irgush basketball player, member of the Soviet national team Uvais Akhtaev, his height is 236 cm;
Alexander Sizonenko, Soviet basketball player with a height of 237 cm;
Gheorghe Muresan is an athlete from Romania with a height of 231 cm;

Many famous athletes are carriers of acromegaly. Among them:

Brazilian mixed martial arts fighter Antonio Silva. Antonio has a large chin and feet.
Andre the Giant is a famous wrestler; with a height of 2.24 cm, his weight was 240 kg.

Among the artists:

American actor Richard Kiel, his height is 218 cm;
TV presenters French twins of Russian origin Bogdanov;
American actor Matthew McGrory, his height was -229 cm
Big Show is an actor and wrestler with a height of 2.13 cm;
Great Kali whose height is 2.16 cm.

The most famous patient with acromegaly is the famous French fighter, world champion Maurice Tillet. Due to the progression of the disease, Maurice was unable to fulfill his dream of becoming a lawyer. Few people know, but it is Maurice who is the prototype of the cartoon character Shrek.

In Russia, the most famous carrier of acromegaly is professional boxer and politician Nikolai Valuev. At one time he underwent surgery to remove a pituitary tumor.