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Cutaneous Manifestations
Typed, undated manuscript.
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Hypo State | Hyper State | Remarks | |
Pigmentation: yellow to bronzing | Addisons
Chronic |
Not produced in experimental animals. Not lessened by any known therapy. In the Addisonian, may be transcent in other type. (produced in one of our animals by taking off lymphatic duct.) | |
Cortical Tumor | One of secondary manifestations of cortical tumors of sex stimulating type during stage of hypo function. Disappears slowly after removal of tumor. | ||
Pseudo anemia | Low functioning adrenal, seen in pampered children | Normal pink color can be secured by adequate doses of cortical extract. Test cases are usually sensitive to sun and do not tan, but after cortin therapy, tan as well as others. | |
Urticaria | Addison
Hypo-function |
Seen in the Addisonian and in hypoadrenal states similar to sensitivity to drugs, insulin, toxins, etc. | |
Excessive and odorous perspiration | Hypo states | A cutaneous manifestation of nervous origin. Possibly due to lack of capillary tone of deep structure; rectified by adequate salt intake with or without appropriate glandular therapy. | |
Conjunctivitis | Addison
Hypo states |
In the patient with Addison’s relieved by cortin and adequate salt intake. In hypo states usually accompanied by hay fever; similar therapy. | |
Eczema and other skin lesions, psoriasis | ? | Recent report from Canada recommends use of epinephrine ointment to blanch skin, & soften skin, in conjunction with calamine, etc. Report from Germany recommends use of cortical substance systematically. Independently of these reports, we have used the combination of epinephrine ointment in petrolatum base and cortical substance by mouth. | |
Cutaneous manifestations of cardio-vascular origin | |||
Cyanosis | Hypo state | Insufficient oxidation and circulatory rate. Epinephrine and saline intravenously. | |
Purpura | Usually accompanies adrenal | Most remedial measures are usually of no avail as condition is more often bilateral or due to hemorrhagic cysts; supports treatment only. However, may be seen in hypo states supposedly due to loss of capillary tone. | |
Gangrene–
angiospastic |
Thromboangiitis obliteran | Supposed to be due to prolonged medullary hyper function. Hypertrophy of muscular coat of vessels and contraction; relieved by unilateral suprarenalectomy and sympathectomy. | |
Transient angiospastic | Usually due to medullary tumor. Treatment, sympathectomy. | ||
Hypodermic of epinephrine | Epinephrine given in doses of 1-10,000 and less will sometimes cause necrosis and sloughs. | ||
Cardio Vascular.
Faint heart sounds. Small heart muscle. Low blood pressure. Palpitation Tachycardia Dyspnea (cardiac) Vertigo Fainting attack Chilliness |
Addison’s disease.
Amyloidosis of adrenals. Metastatic tumor Sclerosis of adrenals. Other hypo states. |
These are cardinal symptoms of Addison’s disease and are seen in the other hypoadrenal states mentioned. These are a result of lowered oxidation rate causing a general hypotonia with the attendant lowering of the circulatory volume and rate. Blood pressure is usually low–60/100 but may be over 140. To compensate for low volume, tachycardia is frequently present but the stroke seems ineffectual. Treatment, cortin and salt. | |
Shock | Acute episode | Many of the above can be classified as shock symptoms such as low blood pressure, tachycardia. This is usually transient. Epinephrine by intravenous route in saline, 1-50,000 or 1-100,000. | |
Splanchnic dilatation | Hypo states | Usually accompanied by pale alabaster skin condition frequently chronic. Cortin and salt. | |
Hypertension
Low Blood Value |
Medullary overfunction or tumor | Attacks may be noted of transient character lasting from 2 minutes to several hours accompanied by tachycardia, feeling of constriction, fear, loss of and transient glycosuria, without necessary blood sugar use. Attacks may be continuous with blood pressure up to 300 mm. Hg.
Treatment: removal of tumor or partial cortex adrenalectomy. |
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BIO Chemical | |||
Loss of no concentration of blood | Experimental
Addison’s Hypo states |
Loss noted in both totally adrenalectomized animal and Addison’s disease and other hypo-states. If entire cortical adrenal function is not destroyed, adequate sodium chloride intake may be sufficient. In total destruction use of cortin is augmented by Sodium Chloride intake. | |
Loss of Cl5HCO3 | Experimental
Addison’s Hypo states |
Same as above. | |
Increase of | Experimental and Addison’s | Some have postulated that the effect is to a degree responsible for the cardiac disturbance. It decreases to normal with cortin therapy augmented by adequate sodium chloride intake. | |
Increase in non-protein nitrogen | Experimental and Addison’s | Non-protein nitrogen figures may be as much as ten times the normal in dogs dying from adrenal insufficiency, and reach very high levels in the Addisonian. | |
Decrease in blood sugar | Experimental, Addison and Hypo states | Accompanied usually by low rise in tolerance. | |
Glycosuria | Medullary, hyperfunction and tumor | May be permanent but is usually transient. Suprarenalectomy or removal of tumor. | |
Loss of Plasma volume | Addisons, amyloid degeneration. Experimental animals. | Loss due to increase in urination at initial period of insufficiency. Quickly improved by cortin and salt. | |
Basal O2 consumption | Experimental. Addisons
Amyloid & hypofunction |
Lowered basal rate may not appear until late in Addison’s disease or hypo states. It may be compensated for by other ways in amyloid degeneration. In the suprarenalectomized animal, it drops rapidly after the 4th day. Corrective measure, cortin and salt. | |
Hyperfunction of medulla or tumor. | Causes increase in b.m.r. It may be temporary and recurrent or may be fairly constant simulating thyroid disease. Removal of tumor or unilateral suprarenalectomy & sympathectomy. | ||
Increase in plasma protein | Experimental
Addisons Hypofunction states |
Increase in elements too is noted as well. Relieved to normal by cortin. | |
Blood lipins | Addisons | Sometimes slightly increase. | |
Anemia | Addisons
Hypostates |
Hyperfunction of medulla | Anemia in these cases is rare, contrary to Addison’s first description; however in states of hyperfunction of the medulla, a secondary anemia that readily responds to massive iron dosage is present. |
Creatinuria | Addisons
Experimental |
A terminal condition seldom benefitted by therapy. | |
Gastro-intestinal symptoms | |||
Constipation
Diarrhea Hypertonia Hyperchlorhydria Hypochlorhydria Atonia Achylis Peptic Ulcers Duodenal ulcers Pseudo angina Anorexia Nausea Vomiting Belching Tympanitis Epigastric pain Emaciation Relaxation of Muscles |
Addisons
Suprarenalectomy Hypo states |
Constipation is the rule in the Addisonian, but in terminal cases there may be a diarrhoea. This constipation is frequently seen in hypo states and can be adequately taken care of by the administration of sodium chloride. In the Addisonian salt may or may not be sufficient, but the addition of cortin quiets the condition. In the early stages of the disease, hypertonia is present with a hyperchlorhydria and a spastic colon and a hypermotility of the small bowel, and stomach. During this period there is frequently reported an insatiable appetite. Finally this passes into a hypochlorhydria and hypotonus, spasticity of the colon, passing off more gradually and finally achlorhydria or atonus with the attendant constipation which at times even sodium chloride and cortin require aid form posterior pituitary extracts. In the early stages nauseous is frequently present with tympanitis and belching symptoms which progress with the disease. Early peptic and duodenal ulcers may be seen less frequently in the middle or terminal stages when the pseudo peritonitis symptoms are more prone to occur. Here frequently cases have been operated on for supposed intra abdominal pathology, most frequently appendicitis, for the pain is usually primarily epigastric. Hiccough too may be present with the condition making an extensive peritonitis seem real. Rigidity of the abdominal musculature may or may not be present in these episodes. | |
Hemorrhage
Toxic |
The hiccough too may be a prominent symptom of damage due to acute toxic processes or adrenal hemorrhage. In the atonic stage of the disease actual shrinking of the oesophagus, stomach and intestinal tract has been reported. In this stage anorexia is always present and nausea and vomiting, not forceful but more of a drooling becomes a prominent part of the gastro-intestinal picture. | ||
Hyper-cortical | In the cortical tumors there is sometimes a diarrhea with an increased demand for food. If however the tumor progresses the typical symptoms of the Addisonian set in. Removal of the tumor is the only remedy. | ||
Hyper-medullary | In the hyper medullary type of tumor actual spasms of the intestine may set in at the time of attack. This is characterized by left epigastric pain. During this period, anorexia is present. These patients are usually severely constipated. | ||
Vomiting of pregnancy | ? | This condition can be relieved in many instances by cortical extract and salt, therefore adrenal damage has been postulated as a possible cause. | |
Gastric cramp | Injection of epinephrine | 1/16 gr. of epinephrine when injected on an empty stomach frequently produces severe gastric cramps. This cramp starts in the upper left quadrant and radiates down toward the umbilicus and lower right quadrant. According to S. Levy Simpson it is a contraction of the jejunum. | |
Cortical | The ingestion of cortical material on an empty stomach also causes a gastric cramp. This cramp however seems to be located more in the right upper quadrant. Both are extremely severe. When whole raw glands are ingested the cramps are so severe, and generalized throughout the abdomen, that it is very difficult to locate any single pain. The cortical pains can be induced by intravenous administration of cortin. Nausea and vomiting sometimes follow the use of the cortical extract. The gastric cramp can be avoided by giving a diet rich in non-precipitated hydrophilic colloids such as raw meat, gelatin, milk, etc. Carbohydrates, fruit juices etc., augment the pain. | ||
Appetite | X | X | Patients placed on cortical extract for hypoadrenal states frequently report a marked increase in appetite with resultant gain in weight. This however, is followed by a lessened demand over their normal for food, still maintaining or gradually increasing their weight. |
Loss of libido
Impotence |
Addison
Hypo states |
Hyper states | Loss of libido and impotence may be present early or late in the Addisonian. It usually develops late in cortical tumors. In assumed hypo states the administration of cortical extracts and whole raw gland (this fraction is possibly separate from the life-sustaining principle) has to our knowledge resulted in pregnancies in 5 cases where there had long been sterility and no contraceptive measures had been followed. |
Shift in puberty | Cortical tumor | In hypo states puberty is sometimes delayed. It is possible that cortical extracts may help bring on delayed start of menstruation in girls. We have a suggestive case in our records. On the other hand, cortical tumors have been responsible for precocious puberty as early as 5 years. | |
Pseudohermaphrodites: mascularising female, feminizing male
Homosexual precocity, male and female Heterosexual precocity in female |
Cortical tumors | The disturbance of sex characteristics caused by cortical tumors depends somewhat on the time the abnormal growth sets in. If it is congenital in origin, it is sometimes almost impossible to tell the sex of an infant. Male children may apparently have the external genitalia of the female and vice versa. If it develops in childhood, in the male the infant Hercules type is a result. In the female menstruation may begin as early as 5 years. Tumors later on in life are far more frequently found in the female. Here the woman grows a beard. She first of all has great energy, which gradually passes off and if not treated may develop the Addisonian syndrome. Besides the phenomenon of hypertrichosis, she develops a masculine voice and general features change to the male type. In the male, the changes are less predominant, being unusual growth of hair over body, increase of strength at first gradually going away. Surgical removal of the tumor when possible is the only treatment of these cases. They are usually benign growths but may be carcinomatous. Early in the development of these tumors, either male or female may have tremendous increase of libido. | |
Loss of menstruation | Addison
Amyloid |
Cortical tumors | Menstruation loss is frequently seen in chronic tuberculosis where amyloid generation sets in. It also develops in Addison’s disease and in diseases of the cortical tumors. In the first two, cortical extract aids in bringing a return of the functions. In the latter, removal of the tumor is sometimes effective. |
Change in menstrual cycle and painful menstruation | ? | In some cases of postulated hypo states where there has been profuse bleeding, pain or irregularity we have given the cortical extract or cortical extract and epinephrine by mouth. The epinephrine is given to relieve the menstrual cramp while the cortical fraction to regulate. Here we may see two things, shortening of duration to 3 or 4 days with normal flow, or lessening of the menstrual cycle to 21 to 26 days. | |
Polyuria | Experimental | Polyuria follows second suprarenalectomy; the state is also noted in withdrawing cortical extracts when treating cases of supposed adrenal hypo function. | |
Abortion
Absence of lactation Degeneration of testes Atrophy of seminal vesicles Atrophy of ovaries Atrophic changes in pituitary |
Addison’s
Suprarenal |
The reproductive functions are disturbed in Addison’s disease. On adequate therapy (cortin) these functions partially return to normal, provided the condition has not existed long enough to cause complete degeneration of function of part of the organs involved. In states of assumed hypoadrenia, fertility has resulted from adequate cortical therapy in previously barren subjects. | |
Hematuria | Medullary tumor | In certain cases of apparent adrenal tissue found in the kidney, small cysts develop, causing extra evacuation of blood and hematuria. This condition may precede a malignant hypernephroma supposedly of adrenal origin. | |
Pain in back | Addison’s
Hypoadrenia |
Cortical & medullary tumors | Pain in the back is a fairly constant accompaniment of all adrenal dysfunction. It has sent female patients with Addison’s disease to the operating table and in hypo cases with their accompanied menstrual disturbance adequate cortical therapy relieves the hypo state, while surgery cares for the other. |
Neurological Symptoms | |||
Mental asthenia
Poor concentration Irritability Nervousness Anxiety Personality change Insomnia Depression Mental prostration Delirium Coma |
Addison’s
Amyloid Hypo states |
As the Addisonian develops his mental symptoms, they may first be noted as an increased irritability with lack of concentration. As it develops he becomes very restless, his personality changes from one of cheerfulness to one of despair. He suffers from insomnia. Becomes very dull and may develop psychosis of persecution. He becomes very introspective; as his disease continues he enters into a state of mental prostration where even thought is an effort and he may lie for hours in a daze. As the condition becomes terminal, a period of muttering delirium sets in, finally coma, and death. | |
Mental alertness
Increased sociability Personality change: fearlessness, increase ability to concentrate, general feeling of well being, increased ability to sleep |
In contrast to the above is the effect of feeding 5 gms. of whole raw adrenal to normal subjects. Besides its physical energizing properties, it also is a neuropsychic energizer. The personality change is toward extraversion; there is great desire for work; efforts of all kinds are easier. One breathes freer and feels as all the world were his. | ||
Spinal cord degeneration | Addison’s | In cases of long-standing Addison’s disease, degeneration of the lateral and pyramidal tracts may set in; once established, no therapy is effective. | |
Neuro-muscular pain | Addison’s
Hypoadrenia |
The neuritis of the Addisonian is frequently very painful. Likewise it is seen in cases of amyloidosis; illness, such as cancer, arthritis, tuberculosis etc., active cortical extracts and those such as the Coffey-Humber not active in life giving principle, give relief from certain of these painful episodes. Severe pain in extremities may be Forerunner of oncoming Bergers disease with its intermittent claudication; here lateral suprarenalectomy and sympathectomy is the treatment. | |
Hyperesthesia and hypothesia | Addison’s | The Addisonian on occasion presents areas of hyper and hypothesia. These are usually accompanied by spinal cord changes. The pain is allayed by cortical treatment, but underlying pathology is not aided. | |
Respiratory Symptoms | |||
Hoarseness
Pain on speech Choking sensation Costo-vertebral tenderness Asthma: pulmonary dyspnoea Shallow respiration, rapid respiration Bronchial rhonchi: Chronic bronchitis Constriction of chest Susceptibility to pneumonia and respiratory infection |
Addison’s
Suprarenalectomy |
Although gastric, genitourinary, neuropsychiatric, and general symptoms of Addison’s disease are freely discussed by various writers little stress is laid on the pulmonary side of the disease; except by the experimenters who find that pneumonia and lack of resistance to respiratory infections is their most serious problem in preserving their animals. The above tabulation is therefore gleaned more from reported histories rather than the writing of others. | |
Colds | X | Where the adrenalectomized animal is more sensitive to respiratory infections than usual, we have found that adequate dosage of cortical hormone orally and by hypodermic injection will frequently abort colds in the early stages. If, however, they have set in, the toxic symptoms are largely relieved and the duration lessened. In true influenza the post-influenza drag is eliminated. | |
Yawning
Stretching Gasping for air Air hunger |
Addison’s
Hypo states Amyloidosis |
Yawning, stretching, gasping for air etc., are all symptoms of lack of proper gaseous interchange and are frequently seen in Addison’s disease. They disappear under cortical therapy. | |
Relief of cough, loose sputum
Bronchospasm |
X | Oral administration of epinephrine on a full stomach acts as an excellent broncho-sedative. The effect is prolonged. Bronchospasms apparently relax. Sputum becomes more watery and is easily expectorated. The effect of a single dose usually lasts till the next meal. Only in the most severe cases do extra doses have to be given. | |
Asthma | ? | This is also effective in asthma even in cases when by hypodermic injection, reversal of effects have been obtained. However, in conjunction with the cortical fraction, it is far more effective. In the asthmatic too it apparently helps to control the fundamental bronchitis and the emphysema seems to be rapidly lessened. In severe asthmatic children of 2 to 10 years standing, whom no other relief measures seem to have helped, apparently gradually lose their emphysema and bronchitis. |