What are the hormones of gigantism

This representation was made by Ms. Priv. Doz. Ursula Plöckinger, Charité, Universitätsmedizin Berlin, Campus Virchow-Klinikum. It is intended for laypeople, but in no way can it replace a discussion with a doctor. Only this person can assess all the details of the respective personal case, provide further individual clarification and initiate necessary diagnostic and, if necessary, therapeutic measures. The information given here corresponds to the state of knowledge in mid-2004. New findings can make parts or the entire presentation out of date.

Acromegaly is caused by a (benign) tumor of the pituitary gland (pituitary gland) that releases growth hormone in an increased and uncontrolled manner. An increased secretion of growth hormone (somatotropic hormone [STH], often also English growth hormone [GH]) leads to the clinical picture of acromegaly. If this happens already in childhood, it becomes gigantic (gigantism). The frequency (incidence) is 3-4 patients / million / year. In Germany, this corresponds to around 250-330 new cases per year. There are around 3000-6000 patients in Germany with this disease (prevalence). It usually takes about eight years from the onset of symptoms to diagnosis. The physical changes are minor at first, as the characteristic clinical picture develops insidiously, without sudden changes in the external appearance. The diagnosis is then often made by chance, e.g. when changing doctor. Then there is usually already the full picture of the acromegaly. The chances of a cure are then - compared to a diagnosis in the early stages of the disease - already significantly lower. In very rare exceptional cases, acromegaly can have a cause other than a pituitary tumor (less than 1% of patients).

Clinical picture and symptoms

Acromegaly is most commonly diagnosed between the 3rd and 5th decades of life. Patients who appear strong complain of rapid fatigue, reduced physical resilience, poor concentration, increased tendency to sweat, often headaches and occasionally diffuse joint problems. The change in the skin - it is thickened, shows a clear tendency to perspire and increased sebum secretion (seborrhea) - is often not perceived as pathological. The characteristically warm, moist hand of the acromegalic patient with a slightly increased consistency is widened and plump. Changes in the connective tissue and the bones lead to the specifically acromegalic facial features with pronounced forehead wrinkles, deep wrinkles around the mouth and the prominent protrusion of the eyelid ridges. Further symptoms can be a carpal tunnel syndrome (abnormal sensations in the first three and a half fingers of the hand due to pressure on the median nerve in the wrist), as well as snoring and sleep apnea syndrome (short breathing pauses during sleep). Other typical signs of acromegaly include the teeth spreading in the lower jaw, enlargement of the tongue, and a deep voice. Secondary diseases are often diabetes, high blood pressure and joint changes. The mass in the pituitary gland can impair the function of the healthy part of the gland (menstrual disorders, underactive adrenal or thyroid glands). When the tumor expands upwards, the optic nerves are impaired with tunnel vision (visual field restriction) and possibly loss of vision.

Diagnostic procedure

As a search test, the determination of the insulin-like growth factor-I (IGF-I) can be used, which is formed in the liver under the influence of growth hormone and which mediates many effects of growth hormone. An age- and sex-specific normal IGF-I concentration does not, however, exclude acromegaly with certainty. The "gold standard" in diagnostics is the sugar exposure test. The administration of sugar (glucose) leads to the inhibition of growth hormone release in healthy people. If no growth hormone values ​​lower than 1µg / L are reached, the diagnosis is confirmed. Then the function of the rest of the pituitary gland must also be checked (pituitary hormones, which are important for the function of the ovaries / testes, the adrenal gland and the thyroid gland). A magnetic resonance imaging (MRI) scan has to detect the tumor in the pituitary gland and determine its size and its relationship to the surrounding structures, especially to the overlying optic nerve junction. If there is a tumor that has grown beyond the sella turcica (Turkish saddle, the bony structure at the base of the skull in which the pituitary gland is located), an ophthalmological examination must be arranged.

Therapy options

Operative therapy
The aim of the therapy is to eliminate the GH excess (GH less than 1 µg / L in the sugar load test, IGF-I normal) by completely removing the tumor. This should be done while maintaining or restoring the remaining pituitary functions (so-called selective adenomectomy). As a rule, a transsphenoidal approach is chosen for this. Adenomectomy is sought (i.e. removal of the tumor through an access through the nose). The success depends on the size of the tumor (and thus also on the timely diagnosis) and the experience of the neurosurgeon. (Indication: more than 30 such operations / year). In experienced hands, the risk of complications is low (less than 1-2%, meningitis, drainage of cerebrospinal fluid [liquor]) and these are usually easy to control. Mortality is below 0.5%. If a microadenoma is present (tumor diameter less than 1 cm), the chances of recovery are 80% and higher. However, if there is a macroadenoma (tumor diameter greater than 1 cm), the healing rate drops to below 50%, and if the tumor is on the side to only 35-45%.

If the therapy goal is not achieved postoperatively, drug treatment or radiation therapy are available as a second therapy. A step-by-step scheme can be used for drug therapy:

Medical therapy
Dopamine agonists (DA) inhibit the release of STH in around 20% -50% of patients with acromegaly. However, normalization of the STH concentration is rarely achieved. DA must be administered gradually. A slowly increasing dosage allows the first success check after 6 weeks and almost completely prevents side effects such as nausea, drop in blood pressure when standing (orthostasis), tiredness and poor concentration. Newer DA (cabergoline, quinagolide) are possibly somewhat more effective and fewer side effects than the first generation DA (such as bromocriptine). Somatostatin analogs (SSA) reduce the GH concentration in 75% of patients by about 50%. Today they are mostly given as long-acting preparations that are injected about every 4 weeks. Half of the patients achieved the therapy goal. The clinical improvement in the patient is often more pronounced than the decrease in the STH or IGF-I concentration. The therapeutic effect cannot be individually foreseen. A therapy attempt for 3 months is recommended. The side effects of the therapy, such as abdominal pain, gas and diarrhea, usually subside after 3-5 days. During therapy, blood sugar levels must be checked and, if treatment has been going on for many years, vitamin B12 must also be checked. The risk of gallstone formation requires regular (every 3 months) sonographic examinations.

Growth hormone antagonist: With pegvisomant, a new therapeutic principle is available for patients who do not achieve a sufficient reduction in the STH concentration with SSA. This is a growth hormone antagonist that blocks the effect of STH in the tissue (a so-called receptor antagonist). 98% of the patients achieve a normal IGF-I concentration. However, experience with this therapy is still limited. Therapy may be accompanied by an enlargement of the tumor, so appropriate monitoring (MRI) is required. Watch out for an increase in liver enzymes.

radiotherapy
If the measures mentioned do not lead to the desired success or if the tumor grows again, radiation therapy is possible. It lowers the concentration of growth hormone by about 10% per year. If the initial concentration is high, the STH values ​​are then increased for up to 10 years or more. This period must be bridged with additional drug therapy. The most important side effect is the occurrence of an underactive pituitary gland years after the radiation. Irradiation-related secondary tumors are possible with a probability of 1-2% within 10 years after irradiation. Vascular complications of the brain can also possibly occur.

Aftercare

All patients with acromegaly must remain under medical supervision for their entire life. Unfortunately, after an initial apparently complete healing, recurrences have been observed even after 10 years or more. Care should be provided in close cooperation between the family doctor and an endocrinologist.