Parlodel

Morbidity

There are about 70 cases of acromegaly per 1 million population, 3-4 repeated cases are recorded annually, but the numbers are relative, because The time from the appearance of the first signs of acromegaly to the establishment of an accurate diagnosis ranges from 5 to 15 years.
Approximately 50% of untreated patients die before the age of 50 years.
The main causes of death are complications that develop with this disease: diabetes, cardiovascular pathology, malignant neoplasms, etc.
Modern diagnosis and adequate treatment of this disease can reduce mortality by 2-5 times.
Most often, the disease is diagnosed at the age of 30-50 years, and is characterized by progressive disability and shortened life expectancy.

Etiology and pathogenesis

The existence of several main etiopathogenetic mechanisms of chronic excess production of GH is assumed:

95% - primary excessive secretion of GH by pituitary adenoma;
2% - GH-secreting tumor of extra-pituitary localization (pancreas, lungs, mediastinum, ovaries);
less than 3% - increased secretion of somatoliberin (with the development of hypothalamic tumors);
tumor-free hypersecretion of somatoliberin by the hypothalamus is also possible due to inflammatory processes in the central nervous system.

The growth of pituitary adenoma leads to disruption of the production of other vital hormones, metabolic disorders develop, and, as a result, there is a disruption in the activity of various functional systems of the body (CVS, CNS, skeletal system, endocrine system), sometimes causing irreversible processes (acromegalic cardiomyopathy, neoplasms etc.)

Physiological regulation of pituitary gland functions

The function of the pituitary gland is controlled by the hypothalamus, which produces:

somatoliberin (stimulates the production of GH)
somatostatin (inhibits the production of GH)

GH acts through insulin-like growth factors that are produced in the liver. The main one is IGF-1.

Diagnostics

clinical examination
x-ray examination
MRI
laboratory examination (level of growth hormone and IGF-1 in blood plasma).

Clinical examination

Detection of characteristic changes in appearance, especially enlargement of the hands and feet.
These changes can be noticed even with a slight increase in growth hormone. However, the diagnosis is made on average only 9 years after the first symptom appears.

X-ray examination

X-ray of the skull in lateral projection.
X-ray of the spine, hands, feet.

Obvious signs include:

increasing the size of the sella turcica
double-circuit sella turcica

Laboratory examination

Determination of GH secretion. Normal growth hormone levels are less than 1 ng/ml. An average integrated level of > 2.5 ng/ml is considered diagnostically significant.
Study of IGF-1 blood concentration. This test is the best diagnostic marker, since the only reason for the increase in IGF-1 in the blood is an increase in daily GH production.
Oral glucose tolerance test (OGTT) with 75 g of glucose. The absence of a decrease in the level of growth hormone below 1 ng/ml is a diagnostic criterion for acromegaly.

Advantages of IGF-1 as a diagnostic marker compared to GH

IGF-1 is ultimately responsible for most clinical manifestations of acromegaly;
The IGF-1 level reflects the average GH level for the previous day;
IGF-1, unlike GH, is not subject to fluctuations over a short period of time due to its long half-life;
Even a slightly elevated level of growth hormone is accompanied by a high level of IGF-1.

Treatment Goals

Elimination of clinical symptoms of the disease.
Normalization of GH secretion.
Normalization of IGF-1 secretion.
Elimination of the source of excess HGH production.

Treatment methods for acromegaly

Surgical method

Surgery is the main method of treating acromegaly.
If there are signs of compression of structures adjacent to the tumor, emergency surgery is indicated. In these cases, it is not advisable to recommend preoperative preparation with somatostatin analogues. It is better to use medication after surgery. The probability of success is higher.

But at the same time, if the patient’s condition is unstable, high; there is a risk of complications of general anesthesia (due to damage to the respiratory tract) or there are severe systemic manifestations of acromegaly (cardiomyopathy, severe hypertension, decompensated diabetes mellitus), drug treatment is preferable.

Drug treatment

Somatostatin analogs are inhibitors of GH secretion;
GH receptor antagonists - a new group of drugs that directly block the action of GH and reduce the synthesis of IGF-1 - pegvisomat (Somavert)
Dopamine receptor stimulants - cabergoline (Dostinex) and bromocriptine (Parlodel, Abergin) - are much less effective than the first two groups, but there is evidence that when monotherapy with somatostatin analogues is ineffective, some patients are helped by the addition of dopamine receptor stimulants.

Somatostatin analogues

The half-life of natural somatostatin is less than 3 minutes, so its practical use is impossible.
Long-acting selective analogues of natural somatostatin have been created:
Long-acting octreotide (Octreotide-depot produced by Pharm-Sintez CJSC).
Capable of causing a reduction in the size of pituitary adenomas by inhibiting the proliferation process of both normal and tumor cells.
Therapy with somatostatin analogues not only leads to a significant regression of the clinical symptoms of acromegaly, but also ensures stable control of hormone levels.

Possibility of using somatostatin analogues

Somatostatin analogues are currently the first-line drugs in the drug treatment of acromegaly and are used:

For preoperative preparation 2-3 months in advance;
In the primary treatment of patients who refuse surgery or have contraindications;
In therapy in the postoperative period in case of ineffectiveness of surgical treatment;
When treating patients after radiation therapy until its results are achieved.

OCTREOTID-DEPO

Long-acting synthetic analogue of somatostatin;
A stable therapeutic concentration in the blood is maintained for 4 weeks;
The effect is directly proportional to plasma concentration.

Pharmacological action of Octreotide-depot

Suppresses pathologically increased secretion of GH, as well as peptides and serotonin produced in the gastro-enteropancreatic endocrine system, while the use of the drug is not accompanied by the phenomenon of hypersecretion of hormones through a negative feedback mechanism;
In patients with acromegaly, in most cases it provides a persistent decrease in GH levels and normalization of the concentration of IGF-1/somatomedin C;
Reduces the severity of symptoms such as headache, increased sweating, paresthesia, fatigue, pain in bones and joints, peripheral neuropathy;
In some patients with GH-secreting pituitary adenomas, administration of octreotide led to a reduction in tumor size.

Octreotide depot is used in the treatment of acromegaly:

When adequate control of the manifestations of the disease is achieved through subcutaneous administration of Octreotide;
In the absence of sufficient effect from surgical treatment and radiation therapy;
To prepare for surgical treatment (2-3 months in advance);
For treatment between courses of radiation therapy until a lasting effect develops;
In inoperable patients.

Directions for use and doses

For patients in whom subcutaneous administration of Octreotide provides adequate control of the manifestations of the disease, the recommended initial dose of Octreotide depot is 20 mg every 4 weeks for 3 months. Treatment with Octreotide-depot can be started the day after the last subcutaneous administration of Octreotide.
Subsequently, the dose is adjusted taking into account the serum concentrations of GH and IGF-1, as well as clinical symptoms.
If after 3 months of treatment it was not possible to achieve an adequate clinical and biochemical effect, the dose can be increased to 30 mg every 4 weeks.
In cases where, after 3 months of treatment with Octreotide-depot at a dose of 20 mg, there is a persistent decrease in the serum concentration of GH below 1 μg/l, normalization of IGF-1 concentration and the disappearance of reversible symptoms of acromegaly, the dose of Octreotide-depot can be reduced to 10 mg. In this case, it is necessary to carefully monitor serum concentrations of GH and IGF-1.

Orally, during meals, the maximum daily dose is 100 mg.

Menstrual irregularities, female infertility - 1.25 mg 2-3 times a day; if the effect is insufficient, the dose is gradually increased to 5-7.5 mg/day (dose frequency 2-3 times/day). Treatment is continued until the menstrual cycle normalizes and/or ovulation is restored. If necessary, to prevent relapses, treatment can be continued for several cycles.

Premenstrual syndrome - treatment begins on the 14th day of the cycle with 1.25 mg/day. Gradually increase the dose by 1.25 mg/day to 5 mg/day (before the onset of menstruation).

Hyperprolactinemia in men - 1.25 mg 2-3 times a day, gradually increasing the dose to 5-10 mg/day.

Prolactinomas - 1.25 mg 2-3 times a day, with a gradual increase in the dose to several tablets per day, necessary to maintain an adequate decrease in the concentration of prolactin in plasma.

Acromegaly - the initial dose is 1.25 mg 2-3 times a day, then, depending on the clinical effect and side effects, the daily dose is gradually increased to 10-20 mg.

Suppression of lactation - on day 1, 1.25 mg is prescribed 2 times (with meals at breakfast and dinner), then for 14 days - 2.5 mg 2 times a day. To prevent the onset of lactation, the drug should be taken a few hours after childbirth or abortion (after stabilization of vital functions). 2-3 days after discontinuation of the drug, slight secretion of milk sometimes occurs. This can be eliminated by resuming the drug at the same dose for another 1 week.

Postpartum engorgement of the mammary glands - prescribed once at a dose of 2.5 mg, after 6-12 hours, repeat the dose if necessary (this is not accompanied by undesirable suppression of lactation).

Beginning postpartum mastitis - the dosage regimen is the same as in the case of suppression of lactation. If necessary, an antibiotic is added to treatment.

Benign diseases of the mammary glands - 1.25 mg 2-3 times a day. The daily dose is gradually increased to 5-7.5 mg.

Parkinson's disease - to ensure optimal tolerability, treatment should begin with a small dose of the drug: 1.25 mg once a day (preferably in the evening) for 1 week. The daily dose of the drug is increased gradually, every week by 1.25 mg; The daily dose is divided into 2-3 doses. An adequate therapeutic result can be achieved within 6-8 weeks of treatment. If this does not happen, the daily dose can be increased further - every week by 2.5 mg/day. Average therapeutic doses of bromocriptine for mono- or combination therapy are 10-40 mg/day, but some patients may require higher doses. If side effects occur during dose selection, the daily dose should be reduced and maintained at a lower level for at least 1 week. If side effects disappear, the dose of the drug can be increased again. For patients with movement disorders observed while taking levodopa, it is recommended to reduce the dose of levodopa before starting bromocriptine. After achieving a satisfactory effect, a further gradual reduction in the dose of levodopa can be undertaken. In some patients, complete withdrawal of levodopa is possible.