Hypophysary Cachexia

HYPOPHYSARY CACHEXIA (syn.: Simmonds' disease, cachexia hypophysipriva, dystrophia maranto-genitalis), a distinctive clinical picture with a progressive course leading to severe general emaciation, atrophy of the sexual apparatus, premature aging, and a number of other symptoms, ending in death, most often with sudden onset of comatose conditions. This disease occurs mainly in women (in 90% of cases) - both in adults and children. The first case was described as early as 1856 by Virchow, but the clinical description and establishment of the pathogenic connection with pituitary changes belongs to Simmonds (1914). To date, about 50 cases have been described. Etiology and pathological anatomy. According to Graubner, who collected 34 foreign and personal cases (some of which are in essence not H. c. but pluriglandular insufficiency), the most common cause of H. c. is embolic necrosis with secondary atrophy and sclerosis of the pituitary gland (e.g., in sepsis in parturient women). Infectious lesions play a major role, both in the area of the pituitary gland and the base of the brain. According to Borchardt, syphilis is present in half of the cases (gumma, specific hypophysitis). Tuberculosis of the pituitary gland is not uncommon, either as an isolated disease or as part of a general tuberculous process. More rarely, other infections are encountered as a cause of H. c., or, as in the case of Kufs, cysticercosis. Cases of traumatic origin of H. c. have also been described: rupture of the pituitary gland after skull trauma with transformation of the gland into scar tissue (Reinhardt). Finally, a fairly common cause are pituitary tumors (basophilic adenoma, etc.). According to Simmonds, the most characteristic feature is connective tissue sclerosis of the pituitary gland, mainly of the anterior lobe. However, in some cases no anatomical changes in the pituitary gland are found, for example, in two cases of Simons, where there was only severe vacuolar degeneration of the subthalamic ganglia. Jakob, in two cases, along with changes in the anterior lobe of the pituitary gland, noted proliferation and alteration of glial cells of the ganglia. Zondek tends to explain cases of H. c. without changes in the pituitary gland by the fact that the pituitary secretion does not find suitable physicochemical conditions at its site of action (e.g., in the brain's metabolic centers). A similar phenomenon occurs in Addison's disease with normal adrenal glands. In addition to the mentioned anatomical changes, there is also the so-called splanchmicria (Lichtwitz), i.e., atrophy of internal organs, mostly simple; in addition, senile atrophy of the jaws and teeth is observed. Pathogenesis and experimental study of the disease. Regarding the pathogenic connection between H. c. and its main symptom - cachexia - with the loss of function of the anterior pituitary lobe, doubts have recently arisen among both clinicians and experimenters. Smith obtained in rats after extirpation of the pituitary gland, along with atrophy of various organs, cachexia. On the other hand [the works of Aschner, Arkhangel'sky, etc.], removal of the pituitary gland (particularly in acromegaly) does not always lead to the development of cachexia. At the same time, with preservation of the pituitary gland, damage to the hypothalamic centers can cause cachexia. Extirpation of the anterior pituitary lobe in young animals leads, along with cachexia, to dystrophy of the sexual apparatus; in old animals (and humans), such dystrophy either does not occur at all or is detected much later. However, dystrophy of the sexual apparatus also occurs with damage to the hypothalamus. All this, as well as the aforementioned data of Simons and Jacob, give reason to assume the existence of two independent forms of H. c.: purely cerebral and purely hypophysary, similar to what exists in dystrophia adiposo-genitalis (Frohlich's form and Biedl-Bardet form). Leschke categorically associates cachexia not with the pituitary gland, but with the diencephalon. Mogil'nitsky considers the question of the hypophysary or cerebral origin of cachexia open and cautiously speaks of "hypophysary-cerebral cachexia." Course of the disease and symptomatology. H. c. usually appears at the age of 30-40 years, in women it often begins with menstrual disorders; the disease usually develops over several years. The cardinal symptom is cachexia (in only rare cases is some obesity observed initially, then passing into cachexia). The weight of patients can reach 25 kg. Patients consist literally of skin and bones (see Fig. 1 and 2). An obligatory, although sometimes late, symptom is atrophy of the sexual apparatus. Very rapidly develop signs of premature aging: atrophy of the skin, which becomes dry, wrinkled, inelastic, pale (sometimes resembling scleroderma), graying or loss of hair (including eyebrows), atrophy of the jaws, loss of teeth, trophic changes in the nails. Atrophy also affects internal organs (splanchmicria): the heart is hypoplastic, the aorta is narrow, etc. Blood pressure is lowered. An important symptom is severe adynamia. Complaints of chilliness (body temperature below normal) are common. Hypothyroidism, lack of appetite, vomiting, nausea are observed; more rarely - diarrhea, attacks of painful spasms in the abdomen. Reflex excitability is reduced. From the side of the psyche, lethargy, apathy, loss of memory are noted; more rarely - hallucinatory confusion, epileptic seizures. Sometimes marked drowsiness (lethargia pituitaria) is noted. Anemia is often observed. Protein metabolism is often decreased. The basal metabolic rate, according to some authors, is not decreased; according to Zondek - lower than in any other disease. Special dynamic action of proteins is normal or delayed. Disorders of water and salt exchange are very characteristic, which to a certain extent are opposite to what we see in diabetes insipidus. However, these disorders are not specific - they are observed in all kinds of severe cachexia. In H. c. there is water retention (oliguria) and salt retention. There is no increase in thirst, in the blood - hypalbuminosis, i.e., impoverishment of the blood with proteins. If H. c. is caused by a tumor, then there are also symptoms of a brain tumor (headache, bitemporal hemianopia, choked disk). The course of the disease is usually slow - 10-12 years, more rarely - several months. The course, as well as the symptomatology and outcome, to a large extent depend on the processes underlying the disease (tumors, inflammatory changes, etc.), as well as on age: in case of early disease, along with cachexia, there is also a delay in growth. Diagnosis and prognosis. In severe cases, the diagnosis is made easily already by the external appearance of the patient. Nevertheless, it is always necessary to exclude cachexia of other kinds (due to malignant tumor, shrunken kidney, etc.). It is not always easy to delimit H. c. from pluriglandular insufficiency, especially if symptoms of thyroid insufficiency are added to H. c.: in men, pluriglandular insufficiency is more common, in women - H. c. If, in addition to the usual symptoms of H. c., there are also symptoms of myxedema, tetany, the presence of pigmentation, etc., then this indicates a pluriglandular disease. Sometimes it is difficult to delimit H. c. from Addison's disease, in which there is also cachexia, signs of senile involution, etc. - The prognosis is poor. At present, attempts are being made to isolate benign forms of H. c., i.e., formes frustes (Rey). These forms are allegedly amenable to treatment. Fliess speaks of hypophysary weakness, associated with general adynamia, inability to concentrate attention, neuralgic headaches and an increase, not a decrease, in the total amount of urine. These cases are often associated with the period of sexual development or with the postpartum period. - Treatment. Specific organotherapy in the developed form of H. c. has proved useless; however, it is not excluded that this depends on the unsatisfactory quality of pituitary preparations. However, in animals from which the pituitary gland has been removed, it is sometimes possible to increase weight with the help of organotherapy. Cases of hypophysary cachexia associated with syphilis are amenable to specific treatment. Only in cases of definitely endocrine (as described by Rey) do preparations of the anterior lobe help, and even better - preparations of the anterior and posterior lobes of the pituitary gland.

M. Jewish.