PITUITARY GLAND (HYPOPHYSIS)

General overgrowth of all tissue and organs occurring before closure of epiphyseal cartilages.

Cause. Oversecretion of growth hormone during childhood. Usually due to adenoma.

Signs and symptoms. General overgrowth, before age 15 and over 6 feet tall. Body well proportioned. Strong, alert and intelligent with gentle disposition.

Treatment. None unless adenoma causes pressure symptoms. Optic chiasrna susceptible to pressure causing disturbances in vision and eventual blindness. Destruction of pituitary gland by irradiation or by hypophysectomy. Hormone replacement therapy necessary thereafter.

Complications. Optic nerve pressure. Hypopituitarism later - gland becomes exhausted.

ACROMEGALY

Overgrowth of certain parts of body occurring after closure of epiphyseal cartilages.

Cause. Oversecretion of growth hormone due to adenoma.

Stns and symptoms. Increasing size of head, hands and feet. Bones affected: flat bones of cranium, mandible, phalanges. Enlargement of mandible may interfere with mastication. Organic overgrowth includes, tongue, lips, skin and all internal organs. Psychiatric disturbance common - emotional instability, unreasonable behaviour, depression, persecution complex.

Atrophy of adrenal glands leading to Addison's disease (p. 136). Extreme loss of weight. Muscle weakness. Sensitivity to cold.

Diagnosis. Confirmed by detecting absence of hormones from thyroid, gonads and adrenal glands. Low plasma protein-bound iodine (P.B.I.) Low uptake of radio-active iodine by thyroid gland (R.A.I.). Lowered metabolic rate (B.M.R.). Low urinary hydrocortisone and gonadotrophin. Normochroniic anaemia. Extreme sensitivity to insulin. X-ray of skull may show tumour or abnormality of pituitary fossa.

Treatment. Ideally this would consist of stimulating the thyroid, adrenal and gonad glands with their respective trophic hormones. Unfortunately T.S.H. and A.C.T.H. need to be - injected daily and gonadotrophins set up an immunological response in time. Hence, treatment consists of giving thyroxine, cortisone, testosterone and oestrogens. Thyroid extract orally 15 mg daily increasing to 120 mg daily over several weeks.' Cortisone

5 mg daily increasing to 30 mg. Testosterone cyclopentyl proprionate 100 - 200 mg every 3 - 4 weeks.

Complications. Water intoxication following excess fluid intake due to cortisone which liniits rate of excretion of water. Excessive appetite and obesity also due to cortisone. Addisonian crisis if thyroid extract given in too large a quantity before instituting cortisone therapy. Compression of optic chiasma leading to blindness.

FROEHLICH'S SYNDROME

Obesity and genital atrophy.

Cause. Anterior pituitary insufficiency secondary to hypothalarffic disorder.

Signs and symptoms. General adiposity. Underdevelopment of secondary sexual characteristics and sexual organs. Occasionally mental retardation, lethargy and knock-knees.

Treatment. If presence of tumour can be established - deep X-ray therapy.

CUSHING'S SYNDROME

Primarily a disease of the adrenal glands (p. 136). Occasionally the oversecretion of cortical hormones is due to an oversecretion of A.C.T.H. Such patients often have deep pigmentation of skin.

Treatment. Extirpation of pituitary gland by deep X-ray therapy or hypophysectomy.

OXYTOCIN INSUFFICIENCY

Oxytocin production normally increases during last days of

pregnancy. When this fails to occur, labour is prolonged and uterine contractions poor. Oxytocin also produced in response to babe suckling and causes release of accumulated milk into alveoli leading to nipples. Insufficiency of oxytocin causes retention of milk which inhibits production of lactogenic hormone (lutcotrophin, prolactin), thus niilk production ceases. While lactogenic hormone is being produced, follicle stimulating hormone and luteinising hormone is suppressed, so that ovulation and menstruation do not occur.

DIABETES INSIPIDUS

Passage of large quantities of pale urine containing few solutes and hence of low specific gravity. Intense unquenchable thirst (polydipsia).

Cause. Defect in chain of events leading to release of anti-diuretic hormone (A.D.H.) from posterior pituitary. A.D.H. secreted in hypothalamus, conveyed to posterior pituitary and released on receipt of impulses from special centres in hypothalamus which are sensitive to concentration of solutes in blood (osmolality). Injury to these centres is the prime cause of diabetes insipidus - trauma, tumours, meningitis, cerebrovascular accident.

Signs and symptoms. Passage of large amounts of pale urine, 10 - 20 litres per day. Specific gravity below 1005. Insatiable thirst (stopping drinking does not stop the polyuria). Severe dehydration occurs rapidly if patient unable to drink - unconscious, anaesthetized etc.

Diagnosis. Condition easy to diagnose. Cause may be difficult to trace. Hickey-Hare test - intravenous infusion of hypertonic saline causes increase in urinary output; administration of 0.2 -

0.3 rid of A.D.H. decreases output. Exhaustive tests to find cause - lumbar puncture, X-ray of skull and chest for metastatic cancer, Wassermann and Kahn for syphilis, marrow biopsy for multiple mycloma.

Treatment. Correction of underlying cause if possible. Specific treatment - intramuscular injection of vasopressin tannate in oil 0.5 - 1 nil. Effect is immediate and lasts 24 - 72 hours. (Active ingredient tends to settle as thick sludge at bottom of ampoule. Patients on self administration must learn to warm the container and shake it thoroughly before injecting). Posterior pituitary snuff may be inhaled 2 - 3 times daily but is intensely irritant to mucosa causing rhinitis, pharyngitis and even tracheitis and gastritis. 8-lysine vasopressin, a synthetic substitute, may be inhaled from nasal spray 30 - 60 mg daily.

THYROIDGLAND

BENIGN GOITRE

Enlargement of thyroid gland without oversecretion of thyroxine.

Cause. Continual lack of iodine in drinking water and food reduces thyroxine production, which causes an increase in secretion of thyrotrophin from anterior pituitary gland. Excess thyrotropffin causes hyperplasia of thyroid gland.

Types. 1. Adolescent. Temporary enlargement in response to greater demand for thyroxine at puberty.

2. Endemic. Lack of iodine in certain areas of the world. (Largely combated today by addition of iodine to salt.)

3. Colloid. When iodine deficiency corrected large amounts of colloid are made and stored.

4. Nodular. Pressure of colloid inside vesicles may cause destruction of cuboid cells. Replaced with fibrous tissue which gives nodular feel.

5. Cystic. Vesicles may coalesce due to breakdown of intravesicular cells.

Signs and symptoms. Swelling of neck may be only symptom. May press on trachea causing dyspnoca especially when lying flat.

Retrosternal goitre may cause dyspnoca, respiratory stridor, dysphagia. Attack can be fatal.

Treatment. Small soft new goitres tend to disappear on administration of iodine. Lugol's iodine 0.5 - 1 rnl daily in divided doses., Old, established goitres will not regress. Iodine should be adnfinistered with great caution as the greatly increased amount of tissue will take up large quantities of iodine and convert to thyroxine while the blood levels of thyrotrophin are high. Very small doses 0.1 nd may be given on alternate days. As output of thyrotrophin falls, doses can be increased.

Retrosternal goitre should be excised.

Complications. Pressure on surrounding structures - trachea, oesophagus, recurrent laryngeal nerve. Haemorrhages into vesicles especially in cystic type - characterized by sudden asymmetrical enlargement of gland. Thyrotoxicosis. Hypothyroidism.

HYMTH'YROIDISM

Undersecretion of thyroxin.

Types. 1. Congenital (cretinism).

Cause. Insufficiency of thyroxine due to (1) failure of thyroid gland to develop; (2) failure of pituitary gland to secrete thyrotropffic hormone; (3) maternal iodine deficiency during pregnancy; (4) in some cases - failure to convert colloid into thyroxine in spite of higher than normal ability to take up iodine.

Signs and symptoms. Often missed until child is about 6 months old but keen observation may detect them much earlier. Skin - coarse, dry, sallow; hair - scanty and dry; eyes - narrow, slit4ike and set wide apart; nose - broad and flat; mouth - wide pendulant lower lip; tongue - large and protruding; neck - short, thickened with pad of myxoedematous tissue across shoulders; back - lordotic; appearance - cross; temperament - soen, lethargic, disinterested.

Others - umbilical hernia common. Pot belly. Constipation. Delayed growth, dentition, and closure of fontanelles. Temperature subnormal. Pulse slow.

Diagnosis. Confirmed by low basal metabolic rate. Low plasma

protein-bound iodine. Low uptake of radio-active iodine (may be higher than normal in few cases).

Treatment. Immediate administration of thyroid gland or thyroxine or one of several synthetic thyroid equivalents. Dried thyroid gland usually achieves good results. Is cheap and can be taken orally. Thyroxine and its equivalents are extremely powerful, 1000 times more so than thyroid gland, and dosage is not as easy to stabilize.

The longer diagnosis and treatment is delayed the less chance there is of reversing mental retardation.

Dried thyroid gland is started at 1 5 mg a day and increased to the maximum non-toxic level by 1 5 mg every 3 weeks. Under one year maximum is about 60 ing daily; 2 - 6 years 90 mg daily; over 6 years 120 mg daily. Toxic symptoms - tachycardia, irritability, failure to gain weight or loss of weight, diarrhoea, sweating. Replacement therapy must continue for life.

Reduced secretion of thyroxine starting after general growth and mental development has taken place.

Cause. 1. Minizry. Atrophy of thyroid gland (may be result of auto-inimune response). Thyroidectomy. Radio-active iodine therapy. Deep X-ray therapy. Excessive iodine ingestion over long period.

2. Secondary. Lack of thyrotrophic horrnone (usually associated with lack of other anterior pituitary gland hormones. (p. 1 14).

Stns and symptoms. Typical facies - dull uninteresting expression, puffy eyelids, alopoccia outer third of eyebrows, Creamy poor of skin. Dry, thickened, rough skin. Subcutaneous tissues indurated with fluid containing much protein (hence name - myxoedema. Myxa, Greek = mucus). Hair dry, straight and sparse. Tongue enlarged. Speech slow and slurred. Voice hoarse. Mental dullness, apathy. Disinclination for mental or physical effort. Capillary fragility and tendency to bruise easily. Menstruation prolonged. Pericardial effusion common. Constipation. Subnormal temperature and slow respirations which may be severe enough to cause coma. Occasionally psychosis (myxoedema madness). Nonnocytic anaemia.

Diagnosis. Confirmed by low rnetabolic rate. Low plasma protein-bound iodine. Low uptake of radio-active iodine. E.C.G. changes - flattened or inverted T wave. Elevated serum cholesterol.

Treatment. Administration of dried thyroid gland or thyroxine or synthetic substitute. Dosage, small to start, gradually building up to maximum. Dried thyroid gland 15 mg daily to 90 or 120 mg. In patients with cardiovascular disease or over 40 years dosage should be built up very slowly. Angina pectoris and congestive cardiac failure can suddenly become much worse if blood levels of thyroxine are suddenly raised. Maximum effect of hormone is not reached for 7 - 10 days after commencement and effect lasts several weeks after administration is stopped.

Complications. Untreated case. Myxoedeniic coma with carbon dioxide narcosis due to excessively slow rate of respiration and circulation. (Treated with fast acting hormone, e.g. tri-iodothyroxine 0.1, mg and artifical respiration).

myocarditis.

HYPERTHYROIDIM

Oversecretion of thyroxine. Women more than men (1 0: 1).

Causes. Adenoma of thyroid gland. Oversecretion of thyrotrophin. Possibly a thyroid stimulating hormone other than thyrotrophin (source and nature suspected but not proved). Occasionally (rarely) thyroid tissue present in ovary. Occasionally follows iodine therapy in endemic goitre.

Terminology. Graves' disease. Basedow's disease - after doctors first describing syndrome. Toxic goitre where previously benign goitre oversecretes. Thyrotoxicosis - literally, poisoning with thyroxine. Ekophthalmic goitre - signs and symptoms accompanied by protrusion of the eyes.

Pathology. Thyroid gland usually enlarged, soft and highly vascular. Following iodine administration gland gets even bigger, becomes firm and less vascular. In 16ng standing untreated cases there are widespread changes in tissues and organs - degeneration of muscles, enlargement of heart, fibrosis of liver, enlargement of thymus tissue, decalcification of bones.

cardiac involvement. Excessive release of thyroxine 5 - 7 days after adn-dnistration may cause thyroid crisis.

2. Deep X-ray irradiatiorl Now seldom used. Effect is satisfactory but involves lengthy treatment. Results in nodular goitre poor. '

General care. Hospitalization is not necessary except for initial investigations and pre-operative care or when cardiovascular involvement is severe and close observation is needed until drug therapy well established.

Patient should continue her occupation but should be warned against overexertion. Diet should be rich in protein, carbohydrate, vitarnins and calcium. Adequate rest should be assured, by mild sedation if necessary.

Sudden severe increase in all signs and symptoms.

Cause. Sudden release of large amount of thyroxine into circulation. Almost always a postoperative complication occurring in patients who have not been prepared adequately with antithyroid drugs. Precipitated by adrenocortical insufficiency. May occur in radio-active iodine therapy.

Signs and symptoms. Intensification of previous symptoms. Extreme irritability, hyperpyrexia, severe tachycardia with atrial fibrillation and sometimes heart failure, hypotension, vomiting, diarrhoea, delirium, con-ia.

Treatment. Immediate administration of intravenous glucose 10'Yo hydrocortisone 100 - 200 rng, reserpine to lower blood pressure, thiamine, oxygen tent, tepid sponging or sterner measures to reduce temperature. Pentothal anaesthetic.

THYROIDITIS (RARE)

Inflammation of thyroid tissue.

Types. 1. Specific acute.

Causes. Specific acute - spread of infection from upper respiratory tract. Nonspecific acute - non-infective, cause unknown.

Chronic (Hashirnoto's struma) - possibly auto-inimune response to patient's own thyroxine.

HWERPARATHYROIDISM

Overweretion of parathormone.

Cause. Adenorm 90Yo. Hyperplasia. Carcinoma.

Pathology. Usually one gland only affected. Encapsulated, soft, brown. Embedded in fat.

Stns and symptoms. Muscular weakness, anorexia, nausea, constipation. Polyuria and polydipsia may develop later. Often first clue is renal colic or spontaneous fracture. X-ray shows osteoporosis, cysts, fractures, bony deformities.

Bone marrow depression conunon with anaemia, leucopenia, thromboeytopenia. Peptic ulcer conunon. Deafness. Keratitis. Kidney stones.

Diagnosis. High blood calcium. Decreased scrum phosphate. Increased urinary calcium and phosphate. Intravenous calcium test - in a normal person a sudden load of calcium causes raised phosphate level in blood and urine. In hyperparathyroidism this does not occur.

Treatment. Force fluids. Restrict calcium intake. Explore surgically to locate and remove affected gland. In general hyperplasia all except one gland removed. Postoperatively a large calcium intake is needed as bones take up calcium very rapidly as soon as parathormone level drops.

PANCREAS

Insulin. Passed directly into blood stream where it acts as carrier substance to transport large glucose molecules through small pores of cell men-ibranes. Lack of insulin causes accumulation of glucose in blood. Cells maintain their energy by utilizing di-acetic acid instead. Liver desaturates fats and converts proteins for this purpose. Di-acetic acid produced in excess of needs and constitutes a poisonous substance causing acidosis (ketosis). Proteins not available for cell building so growth and development delayed.

DIABETES MELLITUS

Accumulation of glucose in blood characterized by polyuria, polydipsia and reduced resistance to infections.

Causes. (1) Lack of insulin. (2) Development of anti-insulin substances.

Pathology. Early invasion of beta cells with glucose. Fibrosis of pancreas in some cases. Lack of insidin causes greater mobilization of glycogen in liver. This increases blood levels of glucose which may be sufficient for cells in mild diabetes. As soon as blood level exceeds 1 80 mg %, glucose lost in urine which offsets the benefits of high blood levels. Tissue need for energy sources causes increased breakdown of fats to diaectic acid. Acidosis (ketosis) results. Increased glucose and diacetic acid in urine prevents reabsorption of water by tubules hence - polyuria and polydipsia with dehydration.

Types of diabetes. 1. Pre-nwtutity onset. Patient under 25. Characterized by true insulin deficiency.

2. Maturity onset. Patient over 25. Characterized by high level of insulin in blood but its action is blocked by ar@.ti-insfflin factors (not yet identified).

3. Associated with other hormone diseases. Excess horrnones from other glands have anti-insulin effect - growth hormone, thyroxine, adrenaline.

Stns and symptoms. 1. Chronic state. May be unrecognised for years, then degenerative changes occur and lead to diagnosis - cataract, chronic nephritis, gangrene of toes, arteriosclerosis, cerebro-vascular accidents.

2. Subacute state. Pruritis, skin infections, moniliasis of vagina, constipation, dizziness associated with dehydration, pc)lyuria, polydipsia.

3. Acute state. Diabetic coma often precipitated by infection

(p. 133).

Diagnosis. Urine is pale, of high specific gravity (over 1025), contains glucose, acetone (diacetic acid in freshly passed specimen). Fasting blood glucose raised (normal: 70 - 1 10 mg %; anything over 130 mg % in fasting subject regarded as evidence of diabetes).

Glucose tolerance test. Patient prepared by giving 300 g carbohydrate daily for 2 - 3 days. On day of test, blood taken for fasting glucose level and then 50 g glucose given orally in water. Normally this causes rise of blood glucose to 120 - 130

rng % in first hour but stirnulates production of insulin and level falls to below 80 ing To in second hour. In diabetes level goes on rising to 200 rng % or higher, and does not fall in second hour. Test may be performed with intravenous glucose when reference to gastro-intestinal absorption is not needed.

Intravenous tolbutamide test. Fasting blood sugar taken and then intravenous injection of 1 g tolbutamide in 10 n-d water. Blood taken for glucose level 20 and 30 minutes later. Normal response - rapid fall of blood sugar due to increased manufacture of insulin. Mature type diabetic response - delayed fall in blood glucose. Prematurity type diabetic response - none.

Treatment

Initial stabilization. AIMS. Correction of glucose-insulin imbalance. Maintenance of optimum level of blood sugar, with regard to amount of energy expended, severity and type diabetes.

Patient started on diet and insulin as soon as possible after tests completed. (In severe cases may be necessary to start insulin and diet before tests are completed.) Insulin reserve determined. In prematurity type there is often no reserve and patient needs high doses of insulin daily for life. In maturity type, reserve may be high and patient needs n-dnimal doses of insulin or control may be effected with tablets and diet alone.

Search made for septic foci and corrected if possible - septic teeth, tonsils, gaflbladder, sinuses, urinary tract, lungs.

Patient's weight guides initial quantity of food. Prematurity diabetics often greatly underweight; maturity type diabetics often greatly overweight. Ideal weight, for age, height and type of body structure, is taken from tables and initial diet arranged at 25 calories per kilogram of ideal weight. Variations from this will be arranged later taking into account the energy expenditure which will be required for person to carry on his normal activities.

Insulin started at 10 units crystalline insulin daily and subsequent doses determined by level of blood sugar and amount of glucose in urine. At first urine tested carefully 4 times daily - on rising, noon, before evening meal and on retiring. Aim is to keep blood sugar at about 150 mg 7o and to keep urine with a trace of sugar in the specimen immediately preceding insulin injection. Ideally patient has one injection daily. If amount of

insulin needed exceeds 40 units per day it is better to have two injections.

Types of insulin. 1. Crystalline (soluble, regular). Aqueous solution, clear and colourless. Action starts immediately on injection, reaches peak in about 3 hours, action completed in 5 - 6 hours.

2. Protamine zinc (P.Z.L). Pro~ne added in excess to crystalline insulin. Protaniine delays absorption and spreads effect over 30 hours. (Must not be mixed with crystalline insulin as the excess of protamine converts some of the crystalline to P.Z.I.).

3. Neutral protamine Hagedorn (N.P.H.). Similar to P.Z.1. but amount of protamine added is exactly sufficient to combine with the amount of crystalline. Absorption is delayed and effect continues over 24 hours. Can be mixed with crystalline when both quick and prolonged action are required.

4. Globin InsulitL Globin used instead of protamine. Effect similar to N.P.H. insulin.

5. Insulin Zinc Suspensions. Zinc acetate added. Ultra-lente - similar prolonged action to P.Z.1. Semi-lente - action is equivalent to N.P.H. with small amount of crystalline added i.e. immediate action followed by long continued n-dld action. Lente - mixture of ultra- and senii4ente insulins with action similar to N.P.H. insulin.

It is usual for patients to have a mixture of two of the above, crystalline and a long acting insulin so that effect is continuous. Very large doses of P.Z.1. are contra-indicated because of extremely slow rate of absorption. It overlaps the next day's dose.

INSULIN REACTIONS. Crystalline insulin causes rapid drop in blood sugar. Meal must be taken within half an hour of injection and must contain sufficient carbohydrate to counterbalance effect of insulin.

Slow acting insulins cause a very gradual fall in blood sugar which is counterbalanced by the normal meals. If insufficient carbohydrate in last meal of day, blood sugar may fall dangerously low during early hours of morning. Patient wakes with headache, nausea, confusion and incoordination. Resembles a mod cerebro-vascular incident and may be mistaken for same, especially in diabetics with hypertension and arteriosclerosis

where such an event is not unexpected. Other symptoms - lethargy, sweating, nightmares, palpitation. Patient advised to increase amount of carbohydrate in last meal or to set alarm clock for 2 a.m. and take a snack then. Repeated hypoglyeacniic attacks damage cerebral cortex which is to be avoided at all costs. They indicate the need for re-assesment of case with a view to adjusting carbohydratelinsulin balance. Morning attacks suggest too much crystalline insulin. Attacks in the late evening or early moniing suggest too much long acting insulin. Alternatively there is need for increased carbohydrate in diet especially if attacks are accompanied by weight loss.

LOCAL REACTIONS. May be common at first but tend to disappear. Redness, heat, nodule formation at site of injection. Occasionally there is localized loss of fat and loss of sensation. Generalized sensitivity and anaphylactic shock occurs rarely and usually patient sensitive only to one type of insulin. Changing type, or merely changing brand stops this. Occasionally protaniine causes aflergy and patient advised to change to globin insulin.

Insulin resistance rely occur and requires in excess of 200 units of insulin to maintain control over diabetes. Occurs in conjunction with severe acidosis, liver damage and neoplasm. Such resistance usually wanes as time goes on.

Oral hypoglycaemic agents. Useful only in patient with good insulin reserve. If patient can be controlled on 20 units insulin dafly he can usually be controlled on tablets instead. Between 20 and 40 units daily he may be controllable with tablets and insulin together. Over 40 units daily and in all prematurity type diabetic tablets should not be used.

SULPHONYLUREAS:- tolbutamide, chlorpropaniide. Tolbutaniide (Orinase, Rastinon, Artosin) 1 to 2 g daily. Chlorpropamide (Diabinese) 250 to 500 rng daily. Abrupt change from insulin to sulphonylurea may be made if patient not receiving more than 20 units insulin daily. Combined sulphonylurea and insulin recommended for patients receiving more than 20 units. Careful observation of reaction must be made with any patient who has complications such as hypertension, liver damage, ketosis, infections, surgical procedures, renal disease and peptic ulcer.

P R I M A R Y. Insulin coma. Diabetic coma.

SECONDARY. Degenerative changes in small blood vessels leading to retinopathy, neuropathy, nephropathy, gangrene.

Hyperglycaemia (Diabetic coma, diabetic ketosis). Accumulation of glucose and ketones, (mainly diacetic acid), in blood.

SIGNS AND SYMPTOMS. Gradual onset - days or weeks. Increasing weakness and drowsiness. Laboured deep breathing with smell of acetone on breath. Anorexia, nausea, vomiting. Polyuria, polydipsia, dehydration. Possibly fever and abdominal pain.

Due to dehydration - florid dry skin, decreased blood pressure, weak, rapid pulse, reduced eyeball tension, dry brown tongue.

Urine contains sugar and acetone. Blood sugar raised. (Quick reliable method of determining that blood sugar is raised - Ames Dextrostix. One drop of blood allowed to permeate reagent strip for one minute and then washed under a fine jet of water. Colour change shows presence of sugar in blood higher than 130 rng To).

TREATMENT. Aims. 1. Immediate administration of insulin to reduce blood sugar.

2. Immediate correction of dehydration and electrolyte imbalance.

6. Restabflization.

Insulin. 100 units given at once. May be given intravenously or, to achieve more prolonged effect, 60 units intravenously and 40 units intramuscularly. If after 1 hour blood sugar is still over 500 nig % a further 100 units given intrainuscularly. If between 300 and 500 mg %, 50 units given. As soon as blood sugar falls to 200 mg %, glucose given to cushion effect of further insulin to ensure that patient does not swing over to hypoglycaeniia. It also lessens ketosis more rapidly. Indwelling catheter inserted and hourly specitnens of urine tested. Great care needed once blood sugar has fallen to 200 mg %, sugar in urine is reliable guide to glucoselinsulin balance at this stage. A rough guide is to give 1 g

glucose with each unit of insulin to prevent conversion from hyper- to hypoglycaen-da.

Fluids. Water, sodium, chlorides, potassium and phosphorus may all be deficient in hyperglyeacniia. Hypotonic saline (0.45% saline) given first. In severe ketosis the acid/base balance can be more quickly restored if sodium bicarbonate is added to saline (15 g per litre). In milder cases sodium lactate solution may be used instead.

The administration of sodium rmy cause a serious loss of potassium producing weakness, respiratory distress and irregularity of pulse. Corrected by infusing potassium, generally by adding it to glucose solution when blood sugar has reached 200 mg %.

Urine output should be carefully measured and charted.

Shock. Low blood pressure and other signs of shock may indicate need for intravenous plasma or whole blood before the above measures will benefit patient's condition. Foot of bed raised. Vasopresson drugs such as noradrenaline (Levophed) 4 - 16 mg may be adoed to first flask of intravenous fluid.

As soon as patient able to drink fluids in normal manner without nausea and vomiting, intravenous therapy discontinued.

Patient's airway. During deep coma there is little danger of vomiting but as unconsciousness lightens, danger increases. Many doctors require an intragastric tube to be passed on admission and the stomach aspirated every 15 minutes. As consciousness returns, fluids injected through tube after each aspiration; each aspiration measured to gauge how much fluid has been absorbed.

Infection. Often precipitates diabetic ketosis. Treated with penicillin 1 rnega unit 6 hourly.

When patient has recovered restabilization is needed.

Hypoglycaeniia (insulin coma). Fall in blood sugar to below 70 mg %.

CAUSE. Overdosage of insulin. Inadequate carbohydrate after injection. Inadequate glucose reserves to offset long acting insulin. Sudden utilization of glucose by unaccustomed or vigorous exercise.

SIGNS AND SYMPTOMS. Sudden onset. After crystalline insulin, onset often about 10.30 a.m. as injections usually given at

8 a.m. With long acting insulins onset usually in late evening or very early morning.

Anxiety, sweating, hunger, headache, irritability, irrational behaviour, fine tremor of hands and tongue, later - twitching or convulsions. Skin pale and inoist. Pulse full and bounding. Pupils dflated. Urine free of sugar and acetone. (Empty bladder completely - this specimen rely have been in bladder for some hours and may contain sugar. Wait 5 minutes and collect second specimen.)

TREATMENT. Give glucose at once - orally if possible, or by intragastric tube or intravenously. Recovery is usually sudden, complete and dramatic. Cause of hypoglycaemia should be sought and corrected. Importance of adequate carbohydrate intake to balance insulin must be stressed. Restabilization if attacks are repeated.

Retinopathy. Common complication - as high as 90Yo in diabetics of 1 5 years standing. Dilated retinal veins show beading. Capfilary haemorrhages may gradually destroy rods and cones. Thickening and fibrosis of vitreous humour with detachment of retina. Cataract common. Made worse by hypertension, atherosclerosis and renal insufficiency.

Nephropathy. Degenerative changes in glomerular capillaries and tubules. Albuniinuria rely be first indication. Low blood albuniin may occur causing oedema. Increases severity of hypertension. Eventual renal or cardiac failure with tendency to thrombosis. (Renal threshold for glucose rises thus making difficulties when urine test for sugar is used as basis for quantities of insulin).

Atheroselerosis. Very conunon complication occurring about 10 years earlier in diabetics than in non-diabetics. Arteries of heart and legs affected first, causing coronary occlusion and gangrene of toes.

Neuropathy. Numbness, tingling, shooting pains, cramps, muscle tenderness, aching, weakness and paralysis. Absence of sweating, faintness, dizziness. Incontinence of urine and faeces. Severe constipation.

Stricter control of blood sugar levels may reverse changes. Large doses of vitan-dn B complex and vitamin B 12.

HYPERINSULINISM

Oversecretion of insulin.

Cause. Adenoma of pancreas. Malignant islet cells. Occurs occasionally in rmlignancy of other parts.

Signs and symptoms. Hypoglycaen-iic attacks increasing in severity and frequency. Often associated with long interval between meals or excessive muscular activity. Excessive hunger for carbohydrates. May cause obesity.

Weakness, tremor, nausea, sweating, abdominal pain, faintness, circumoral pallor, palpitation.

Mental reactions - irritability, confusion, aphasia, nystagmus, mania, convulsions.

Repetitions of attacks may cause profound personality changes.

Diagnosis. Fasting blood sugar reduced. Administration of glucose brings blood sugar to normal very rapidly.

Treatment. Subtotal pancreatectomy. Should not be delayed as 209'o are due to carcinoma.

ADRENAL GLANDS

ADDISON'S DISEASE (Chronic adrenocortical insufficiency)

Deficient production of cortical hormones.

Cause. Destruction of gland by infections or metastatic invasion, or surgery. Tuberculosis most commonly - spread from kidney.

Incidence. Comparatively rare. 1 in 5,000 admissions. Any age or Sex.

Signs and symptoms. Insidious onset. Increasing tiredness, weakness, anorexia, nausea, voniiting, weight loss. Increased pigmentation of skin which may extend to mucous membranes. More marked in normally pigmented areas e.g. areola. Quick, deep tanning on exposure to sun.

Multiple freckles may appear.

Diagnosis. Low blood corticoids - less than 8 microgram Urinary 17-hydroxicorticoid low and not increased after injection of A.C.T.H. Scrum sodium and chlorides low while serum potassium raised.

Cause. Adenoma or carcinoma of adrenal gland. Hyperplasia of gland of unknown cause. Occasionally oversecretion of A.C.T.H. due to adenoma of,pituitary. Rarely - cortisone-like substance produced by carcinoma elsewhere in body.

Signs and symptoms. Typical general appearance - round, fat face with mouth curving down at corners; fine downy growtli of hair on face, forehead and upper trunk; increased weight due to peculiarly distributed deposits of fat - upper face, between shoulders and in the omentum; purple striations on skin of abdomen due to breaking down of dermal collagen exposing vascular bed of subcutaneous tissue.

Muscular weakness. Rapid onset of fatigue. Hypertension. Amenorrhoca and slight masculinity in females; atrophy of testicles in males. Patient bruises readily.

Personality changes in two thirds of cases - irritability, confusion, depression, suicidal tendencies.

May be significant oversecretion of aldosterone with sodium retention and consequent oedema and potassium loss. In 25% of cases - diabetes with resistance to insulin. Osteoporosis and spontaneous fracture occasionally.

Diagnosis. Raised urinary 17-hydroxycorticoids. Level of hydrocortisone in blood remains elevated following a 3 - 4 day course of dexamethasone. X-ray following retroperitoneal or, perinephric gas insufflation may reveal twnour.

Treatment. Bilaterial adrenalectomy followed by cortisone therapy as in Addison's disease. When condition is definitely due to pituitary tumour - extirpation of pituitary gland.

HYPERALDOSTERONISM

Oversecretion of aldosterone.

Cause. Adenoma of adrenal cortex. Rarely carcinoma.

Signs and symptoms. Two groups - those associated with low blood potassium and those associated with sodium retention.

(1) Muscle weakness, partial paralysis, tetany, polyuria, polydipsia. (2) Hypertension, headache, en 'larged heart, retinopathy, congestive cardiac failure, renal failure.

Diagnosis. Low serum potassiwn. Raised serum sodium. Persistently alkaline urine. Decreased sodium in sweat and saliva.

Treatment. Excision of adenoma if possible. Bilateral

adrenalectomy with hormone replacement for life as in Addison's disease (p. 136).

Prognosis. Without treatment other than potassium replacement patient dies from renal or cardiac failure. With treatment, progress depends on time elapsed since onset of disease and severity of cardiac and renal damage.

VIRILISM

enzymes concerned with manufacture of aldosterone from stage of chemical similar in structure to sex hormones.

Types. Congenital. In female babies - hypertrophy of clitoris, thickening of labia majora, atrophy of labia minora, growth of pubic hair while an infant. In male babies - growth of penis and pubic hair while an infant, rapid bony and muscular growth so that child is much bigger and stronger than his contemporaries but growth stops at an early age and by puberty he is shorter than others of his age.

Pre-pubertal onset. In females - enlargement of clitoris, failure of breast development and menstruation, pubic hair has male distribution, acne. In males - early sexual development.

Adult onset. Rarely a 'pure' oversecretion in adults, usually associated with Cu~g's syndrome. In females - masculinization, deepening of voice, heavier features, growth of hair on face and chest.

Treatment. Suppression of A.C.T.H. with maintenance doses of cortisone or prednisolone or dexamethasone to reduce patient's output of cortical hormones. Markedly altered genitalia in females may require surgical correction. Adult type treated as Cushing's syndrome (p. 137).

depending on reasons for administration. Maintenance dose in Addison's disease 12.5 to 50 mg daily.

Hydrocortisone. Water soluble - Solu-Cortef. Dosage 5 to 50 rng. May be injected directly into joints. Intravenous dose up to 1 00 mg.

Dexd'methasone. Dose 5 to 10 mg daily.

Prednisone. Dose 1 0 to 1 00 mg daily.

Prednisolone. Dose 10 to 100 mg daily.

Methylprednisolone. Dose 10 to 20 mg daily.

.Trianwinolone. (Similar to Dexamethasone).

to 0.2 mg daily.

Deoxycortone. 2 to 5 mg orally; 2 to 10 mg sublinguafly, 100 to 400 mg implantation.

Choice of preparation depends on effects required. Some have powerful salt retaining properties, others do not. All are relatively safe for short term treatment but all carry possibility of serious side effects for long term therapy (development of Cushing's syndrome from depression of A.C.T.H.); hypertension; perforation and bleeding of peptic ulcers; osteoporosis; aggravation of diabetes mellitus; rapid spread of infections; flare up of old tuberculosis; psychological disturbance; obesity; water retention. Sudden withdrawal may cause adrenal crisis.

Regular cheeks of weight, blood pressure, urine for sugar, E.C.G., bone density by X-ray, faeces for occult blood - necessary for any patient on prolonged therapy.

Uses other than hormone replacement. Rheumatoid arthritis - reduction of inflammation and pain, increased movement. Acute rheurnatic fever - abatement of symptoms especially pain. Bronchffl asthrna especially status asthmaticus. Nephrosis. Haemolytic anaeniias. Ulcerative colitis. Chronic inflammatory condition of eye and skin.

PRAEOCHROMOCYTOMA

Oversecretion of adrenaline and noradrenaline.

Cause. Tumour of adrenal tissue either within adrenal glands or associated with sympathetic chain of ganglia.

Signs and symptoms. Variable. Depends on amounts secreted and whether secretion is continuous or intermittent. Hypertension - sustained or paroxysmal causing headache, dizziness, nausea, voniiting, sweating, slow pulse. Weight loss. Visual disturbance. Severe attack may terminate in pulmonary oedema, ventricular fibrillation, cerebral haemorrhage.

Diagnosis. Hypertension persists on lying flat. Elevated

catecholarnines in blood and urine. Histamine provokes attack of hypertension. Phentolaniine 0.5 mg intravenously causes rapid but temporary fall in blood pressure. X-ray may reveal mass or displaced kidney.

Treatment. Surgical removal of tumour. May require extensive exploration to find all tumour masses. Severe fall in blood pressure may follow surgery and noradrenahne could be on hand. Phenoxybenzamine (Dibenzyline) 10 to 30 mg daily, gradually introduced, blocks action of noradrenaline. Useful pre-operatively and for treatment of inoperable cases.

OVARIAN HYPOFUNCTION

Reduction of secretion of ovarian hormones.

Causes. 1. Primary disease of ovary (frequently one ovary only is affected and the other increases secretion under influence of a greater secretion of gonadotrophins so that no signs and symptoms occur).

2. Both ovaries may be affected and may fail to develop, e.g. from virus infections - measles, mumps, - from surgery, X-ray irradiation.

Types. (1) Pre-pubertal. (2) Post-pubertal. (3) Menopausal.

PRE-PUBERTAL. Signs and symptoms. Failure to develop secondary sexual characteristics - breasts especially. Failure to menstruate. Sterility. Continuation of growth of long bones due to persistence of epiphyseal discs. Other hormonal disturbances often associated - diabetes, adrenal hypofunction, myxoedema, virilism.

POST-PUBERTAL. Signs and symptoms. Amenorrhoca. Sterility. Partial atrophy of genitalia and breasts. Osteoporosis.

MENOPAUSAL. Signs and symptoms. Irregularity of menstruation at 45 - 55 years - amount, frequency, duration. Eventual amenorrhoea. Gradual regression of breasts, vagina and uterus. Sparsity of pubic and axfllary hair. Vasornotor disturbances - hot flushes. Emotional instability, irritability, nervousness.

Treatment. Oestrogen replacement therapy (e.g. diethyl stilboestrol 0.5 - 2 mg daily for 3 weeks followed by one week's rest). Brings about sexual niaturation but sterility remains. Treatment in menopausal hypofunction - rid unless emotional upset is disturbing, then, rWId sedation.

OVARIAN HYPERFUNCTION

Oversecretion of ovarian hormones.

Causes. Tumours of hypothalamus. Tumours of the ovaries. (May be benign or malignant).

Types. (1) Pre-pubertal. (2) Post-pubertal.

PRE-PUBERTAL. Signs and symptoms. When amount of hormone is normal there is premature onset of puberty, rapid skeletal growth which finishes early so that the child is much taller than other girls of similar age but at 1 5 - 16 years is smaller than her contemporaries. Early onset of menstruation and ovulation. (Conception is possible.)

When amount of hormone greatly in excess of normal there is the same early niaturation but inhibition of ovulation occurs and prevents conception.

POST-PUBERTAL. Signs and symptoms. Abnormalities of menstruation - frequent (metrorrhagia), excessive (menorrhagia), irregular.

Treatment. Removal of ovarian turnours.

E~ONADISM

Lack of development of testicular tissue concerned with production of testosterone.

Causes. Lack of luteinising hormone, more appropriately called interstitial cell stimulating hormone (I.C.S.H.) in males. Undescended testes. Klinefeiter's syndrome. Froehlich's syndrome. Destruction of testes by disease, surgery or trauma.

Types. (1) Pre-pubertal. (2) Post-pubertal.

PRE-PUBERTAL. Signs and symptoms. Failure to develop male secondary sexual characteristics. Persistence of high voice. Partial or total lack of body and facial hair. SmaH penis and

prostate gland. Continuaiion of bony growth beyond normal time of closure of epiphyseal discs. Deposition of fat resembling breasts.

Delay in diagnosis common. When both testes are undeseended condition is inevitable unless one can he brought into scrotum before age of 12.

POST-PUBERTAL. Signs and symptoms. Secondary sexual characteristics do not regress once they are established. Sexual desire and performance gradually decline and prostate gland

atrophies.

Treatment. Adn-dnistration of one of the long acting synthetic testosterone substitutes. 1 50 mg intramuscularly every 3 - 4 weeks gradually increasing to 250 - 300 mg monthly. Overdosage indicated by acne, hirsutism, retention of sodium with oedema, aggressive personality. When fault is pituitary tumour, gonadotrophins may be used - 500 - 1,000 units 2 or 3 times weekly.

H'YPERGONADISM

Oversecretion of testosterone.

Causes. Testicular tumour - carcinoma of Leydig cells. Excessive secretion of adrenal androgen. Tumour of hypothalamus.

Signs and symptoms. Little or no change in adults. Pre-pubertal - early sexual development. By 3 - 4 years child may have adult sexual organs, growth of body and facial hair, deep voice. Bony growth is very rapid but stops at early age.

Treatment. Surgical removal of tumours. X-ray irradiation. Methtrexate reported to have favourable effect on some forms of testicular tumour.