Acromegaly
is a word that derives from the Greek and means large extremities, ie akros and
μεγάλος megalos. This description of the pathology finds its explanation in the
fact that for an excess of growth hormone, the latter condition that correlates with the pathology, it determines a disproportionate growth of the whole body,
and a manifest and appreciable growth of the extremities, for which patients present with manoni, therefore a pathological clinical picture derived from the
exposure of the organism to an excess of growth hormone (GH) in the post-puberal age and the consequent increase of insulin-like growth factor, also called IGF-1
(insulin like growth factor type 1), secreted mainly by the liver in response to GH. When we talk about acromegaly, however, we should not confuse the term with
"gigantism", which is rather a condition of growth hormone supplementation, but which occurs before the weld of the epiphyses.
The disease is rather rare and affects only subjects of young age, after 20
years and up to 40; sometimes trafficking in subjects who, by reason of doping,
thinking of fortifying their muscular masses, use growth hormone for this
purpose. The incidence is 3-4 cases in a million, other authors describe up to
70 cases that fall ill of this pathology, while in the US 15,000 people suffer
from it; although the average annual incidence is estimated at 3-4 cases per
million inhabitants.
The acromegalic patient presents a characteristic grotesque facies, with frontal drafts, prominent chin, flat nose, feet, hands, tongue and huge and disproportionate facial bones, as well as organomegaly, that is, by the increase in the volume of internal organs (heart, liver , thyroid, intestine, kidney etc.). Symptoms and clinical signs are slow and gradual and can only become evident after years, at least 7 years, so the disease is devious and can lead to death only if neglected and with complications related to cardiovascular disease or after onset of the pituitary neoplasia: The disease is characterized by progressive enlargement of the acrilic bones, the lips, the hands. Some organs such as the liver, the thyroid and the prostate can enlarge excessively (visceromegaly); in this context the development of cardiac hypertrophy, associated with arterial hypertension and ischemic heart disease, is possible. Other manifestations are macroglossia, dental diastasis, hypercalcaemia (up to 16% of cases), arthritis, galactorrhoea, amenorrhea, sexual dysfunction up to impotence, sleep disturbances such as sleep apnea (60% of cases) and drowsiness , carpal tunnel syndrome. Other metabolic alterations such as diabetes mellitus (25%) and hypertriglyceridemia are also found. The set of these organic alterations leads to an increase in mortality in affected individuals. Since in general the lesion is a tumor that grows on the turtica saddle, then there may be various hormonal deficits due to the condition of hypopituitarism. It is mostly related to damage from crushing the cell lines adjacent to the adenoma. The most easily damaged cell line is the gonadotropin-secreting line, followed by the secreting GH. The most resistant are the thyrotropin and corticotropin-secreting lines.
The acromegalic patient has elevated arterial pressure, stiffening of the
vessels and the heart that pumps against pressure goes against cardiac
hypertrophy and diastolic dysfunction, is present in 30% of cases. Studies have
shown that the aorta is also subject to enlargement. In young patients with
recently occurring acromegaly, there is evidence of: increase in left
ventricular mass, improvement of resting heart performance and decrease during
physical exertion with normal or slightly altered systolic ventricular filling.
Somatogenic hormones play a key role in cardiac development and trophism and the
excess / defect of GH / IGF-1 can induce structural and functional cardiac
changes. GH and IGF-1 receptors are suppressed in cardiac myocytes, IGF-1 causes
hypertrophy in cardiomyocytes in treated rats and delays apoptosis of
cardiomyocytes. Furthermore, GH induces the expression of the oncogene c-myc and
other growth factors and stimulates the transcription of mRNA for IGF-1 at the
cardiac level, which in turn interacts with the specific cardiac receptor,
mediating the growth and increase in contractility of myocytes and the
expression of specific muscle genes. Myocardial histological evaluation shows
interstitial fibrosis and lymphocytic infiltration of the myocardium.
Since in the spinal cord it occurs in the inside of the rachis, the growth of
the bones can lead to the compression of some nerves causing different
neuropathies; likewise at the wrist we can have the carpal tunnel syndrome. The
headache can instead be at the compression operated by the tumor mass that grows
on the saddle at the pituitary level and compresses the adjacent structures,
creating edema and pressure cone for which dopamine analogues (such as
bromocriptine), by virtue of the ability to reduce the size of the tumor, can
eliminate the headache with excellent results. In other cases it is possible
that it compresses the optic chiasm causing hemianopia. The subject turns his
head to center an object he is observing and, if he drives the car, he does not
see to the side. Headache is localized in the retro-orbital region, at the apex,
occipital, more pronounced upon awakening, it responds to common painkillers. It
depends on the stretching of the hard mother of the diaphragm of the saddle.
Every condition of headache, deformation of the skull, the need to change the
size of shoes, hair, gloves, ring must give rise to the suspicion of an
acromegalic condition must make think of encephalic lesions and conduct
diagnostic thinking to instrumental investigations and laboratory.
For example. it is advisable to dose IGF1 which may be high. A random dose of GH
less than 0.4 mcg / l associated with IGF-1 levels in the normal range for sex
and age and in the absence of other pathology allows the diagnosis of acromegaly
to be excluded. Another test is the suppression of GH and IGF-1 after oral
loading with glucose.
• Computerized tomography and magnetic resonance imaging are carried out for a
search for tumor masses at the level of the turquoise saddle.
• Dynamic outpatient electrocardiography, also called "Holter", an examination
that records the ECG for 24 or 48 hours, useful for understanding the cardiac
situation of the subject.
Major causes
In the vast majority of cases it is due to the uncontrolled secretion of growth
hormone by an adenoma of the pituitary gland (95-98% of cases), thus increasing
the concentration of insulin-like growth factor.
This percentage is divided between the various groups of adenomas (granulated
cell somatotropes, the most widespread then to mixed cells and mammosomatotrope
cells)
Minor causes
Other less common causes are several forms of neoplasia that do not affect the
pituitary gland: these include lung carcinoma. The percentage of incidence of
these ectopic forms on average is 2% of cases.Terapia
Makes use of:
• Reverse the growth of the tumor and attack it, taking into account that the
encephalic neoplasms can be treated well, if in expert hands.The treatment is
scheduled surgery, and among the various possibilities the operation of choice
remains the transsphenoidal resection, whose success is very high, 80 but also
90% of cases
• Decrease the severity of symptoms that are related to increases in GH and
IGF-1; analogues of somatostatin are administered, which provides multiple
effects: on the one hand it reduces symptoms by offering relief to patients and
on the other decreases the affected tumor masses.
Drugs used:
• Octreotide acetate (analog of somatostatin, discovered in 1970), much more
potent than somatostatin; the dose to be administered is 50 ug (3 times a day)
and, to extend its duration, is modified with mannitol in a formulation known
as Octreotide LAR.
• Bromocriptine mesylate (dopamine agonist), at high doses to give greater
effects, from 1.25 mg up to 5 mg.
• Pegvisomant (growth hormone antagonist), which has also been tested on
pregnant women and has been shown to transmit the drug in such small parts that
it is not harmful.
• Decrease high mortality (and relative decrease in life expectancy) in
affected individuals
Radiotherapy
It is used as a therapy with a very high dosage, normally 5000 cGy while the
dose increases to double if using treatment with accelerated protons, at such a
high exposure there are several undesirable effects.
Furthermore, if normal surgical treatment is not sufficient, new techniques,
introduced recently, are used, such as GKR (a radiosurgery therapy, where a
particular gamma ray knife is used, for the person involves only a few
undesirable effects.
Prognosis
Depending on the size of the adenomas, if they are of minimum size the
prognosis is good for 70% of cases otherwise the percentage decreases becoming
less than 50%. In a small percentage of people there has been a recurrence, but
after years, hypopitutuitarism can be formed. Because of the heart disease that
may arise, mortality is high.