Postgrad Med J: first published as 10.1136/pgmj.29.330.192 on 1 April 1953. Downloaded from

HYPOPITUITARISM By A. A. G. LEWIS, B.Sc., M.D., M.R.C.P. Physician to the Connaught Hospital and the WoodfordJubilee Hospital Saltwell Research Scholar, Royal College of Physicians (From the Professional Medical Unit, Middlesex Hospital)

Introduction available. It confirms and extends the description Many of the clinical features of hypopituitarism of the syndrome of panhypopituitarism arising were described by Simpson in I872 in his account from post-partum necrosis of the anterior lobe of the symptoms associated with post-partum given by Sheehan in a series of papers. This par- superinvolution of the uterus. The syndrome re- ticular condition is now frequently referred to as sulting from the simultaneous failure of several Sheehan's disease. endocrine glands was described by Claude and In recent years, as the recognition of the Gougerot in I907, but at this time the dominant essential features of the complete syndrome be- role of the adenohypophysis in the endocrine came clearer, and as biochemical tests and hormone system was not appreciated. Douglas Robertson assays for the investigation of suspected cases came to be more used, more interest has been (Ig95b) has recently drawn attention to the paper widely by copyright. by Glinski (1913) describing the association of taken in the less severe degrees of pituitary failure, anterior pituitary necrosis with post-partum and several papers have appeared describing such haemorrhage. Simmonds published his account of cases (Cooke and Sheehan, 1950; Oelbaum, the necropsy of a patient suffering from atrophy of Ig952a). One result of this increased interest has the anterior lobe in I9I4. He did not at first been a clearer understanding of the natural history realize the importance of the small size of the of the disease, many aspects of which have recently thyroid and adrenals, in fact he emphasized that been discussed by Hubble (I952). their histology was normal. In subsequent papers he his of failure, The Hormones of the Anterior Pituitary developed conception pituitary http://pmj.bmj.com/ though in the course of this he stressed unduly The adenohypophysis produces at least six certain features of his cases such as cachexia and hormones: Follicle-stimulating (FSH), luteinis- progeria. It was particularly unfortunate that in ing or interstitial-cell-stimulating (LH or ICSH), the title of two of his papers the word ' Kachexie ' lactogenic or luteotropic, thyrotropic (TSH), should have appeared, for this became inseparably adrenocorticotropic (ACTH) and growth hormone. associated for many years afterwards with the syn- There is increasing evidence that the adrenal drome of panhypopituitarism. cortex secretes more than one hormone and that

In I942 Escamilla and Lisser published an ex- Selye's original conception that the gland pro- on September 26, 2021 by guest. Protected tensive review of the literature, collecting details duces both glucocorticoids and mineralocorticoids of ioi cases of this condition. Their four criteria was correct. Whether his hypothesis that the pro- of severe pituitary deficiency (loss of weight, loss duction of the latter is stimulated by a different of sexual function, asthenia and a B.M.R. below pituitary hormone from the former is also true is -zo per cent.) ensured that at least one of not known, but it appears very improbable. It is Simmonds' original misconceptions would be per- stifl doubtful whether adrenal androgen production petuated. Fraser and Smith in 1941 stated that is stimulated by ACTH or by LH. the nutrition of these patients was usually good. Anterior pituitary extracts also inhibit the This was further emphasized by Sheehan and action of hexokinase in catalyzing the transforma- Summers (I949) in their detailed description of the tion of glucose to glucose-6-phosphate, an in- syndrome resulting from seve*re longstanding hibition'which is opposed by insulin. It has been hypopituitarism. This account was based on 95 claimed (Li, 1952) that growth hormone an- cases in which complete or nearly complete tagonizes the action of insulin and that this may destruction -of the anterior lobe was found at partly explain its diabetogenic activity in animals. necropsy,' and is therefore the most authoritative Although this activity appears to be that of growth Postgrad Med J: first published as 10.1136/pgmj.29.330.192 on 1 April 1953. Downloaded from April 1953 LEWIS: Hypopituitarism 193 hormone itself, the latter always produces growth in i5 cases it was only represented by dense in young animals, not diabetes (Young, I952). fibrous tissue. The female genitalia and ovaries The exact relationship between the growth hor- were atrophic, the endometrium being merely a mone and the glycotropic action of the anterior layer of cubical epithelium. No developing pituitary is therefore not clearly known, but there follicles or corpora lutea were seen in the ovaries. is no doubt that the gland plays a direct part in In males the testes were atrophic and the prostate the regulation of the blood sugar by opposing the and penis small. In spite of the fact that the peripheral action of insulin. weights of the patients were within the normal range, most of the viscera were small. Panhypopituitarism Pathology. In a large number of cases destruc- tion of the anterior lobe follows a severe post- Clinical Features partum circulatory collapse. Sheehan and Mur- In severe longstanding hypopituitarism all the doch (I938) thought that the blood flow to the features described by Sheehan and Summers anterior lobe was reduced at delivery,.and that (I949) are usually present. The most character- circulatory collapse would then favour thrombosis istic picture is seen in women who have recovered in the small vessels, with infarction and necrosis of from post-partum haemorrhage complicated by much of the secretory tissue. They found a re- pituitary necrosis. There is usually a history of lationship between the degree of collapse and the very severe collapse following delivery or manual frequency of necrosis in a series of cases; necrosis removal of the placenta, which required the trans- occurred in seven of the eight with the most severe fusion of several pints of blood. Lactation was degree of collapse. Both collapse and necrosis never established and menstruation and libido were found to be more frequent in multiparae. never returned. Afterwards the patient became The necrosis may be very extensive, only small dull and apathetic, mentally slow and sensitive to islets of healthy tissue remaining. cold, with no interest in running the home, often In other cases there may be scarring, fibrosis or retiring to bed or sitting in front of the fire for cystic degeneration of the anterior lobe for which long periods of the day. Occasionally a psychosis by copyright. no definite cause can be found. Occasionally a has been suspected. The appearance and speech head injury appears to have been responsible. are characteristic, the patient having a forlorn, Sometimes evidence is found of previous destruc- round-shouldered attitude and describing her tive lesions due to tuberculosis, gummatous symptoms in a dreary voice. The face is pale and necrosis, or other granulomata. Syphilis of the flabby, sometimes with a slight yellow tint from pituitary is a rare condition; the subject has re- carotinaemia. The mucosae are pale and the cently been reviewed by Oelbaum (I952b). eyebrows thin. The body hair has disappeared Bleisch and Robbins (1952) collected accounts of apart from some remaining on the labia majora. 50 cases with granulomata involving the anterior The skin is thin and dry, and depigmentation, http://pmj.bmj.com/ lobe, and added four of their own. In many of which gives it a wax-like appearance, is wide- these cases there was other evidence of syphilis, spread. Even the areolae are pale. Erythema ab tuberculosis or sarcoidosis. Occasionally trauma igne frequently occurs on the shins, but the areas appeared to have been the cause, and the pos- are not pigmented. There is no tanning after ex- sibility of primary specific pituitary degeneration posure to sunlight. Pain in the knees and stiffness could not always be excluded. In some cases the are common, and with the apathy and physical sella turcica seems to be at weakness may cause the patient to lie in bed almost

empty post-mortem on September 26, 2021 by guest. Protected examination (' empty sella '). This appearance is as if suffering from a spastic paraplegia. Nocturia probably produced by healing and extreme is the rule, and the patient may notice that she does scarring of a granulomatous condition. not pass large volumes of urine after drinking Other causes of hypopituitarism include sur- during the day. Atrophy of the vagina may lead to gical hypophysectomy and cysts and tumours, severe dyspareunia. Sterility is almost invariable. either in the sella or in its neighbourhood. There is an anaemia, often normochromic. Blood In 76 of the 95 cases collected by Sheehan and pressure may be normal or low. X-ray of the Summers, all the other endocrine glands were chest does not reveal the large heart of myxoedema, certainly or probably atrophied. Only in six of but the E.C.G. may show low voltage curves, the 95 had at least one endocrine gland been sometimes with changes due to hyperkalaemia. definitely normal (endocrine atrophy was present There has been a great deal of controversy and in only half the cases of moderate pituitary misunderstanding about the weight of these damage). The adrenal glands were small; only patients ever since Simmonds emphasized the oc- the medulla and the zona fasciculata of the cortex currence of cachexia. Many of them look thin and remained. The thyroid was small and atrophic; ill, but they are not cachectic or emaciated in the Postgrad Med J: first published as 10.1136/pgmj.29.330.192 on 1 April 1953. Downloaded from 194 POSTGRADUATE MEDICAL JOURNAL April 1953 strict sense. Sheehan and Summers stressed that were below the normal range, being relatively the body weight was not usually abnormal. lower in males. Other authors consider that a moderate loss (2) Insulin tolerance test. Details of this test are of weight is common. In reviewing the de- given by Fraser and Smith (I94I). An attempt is tails of 35 cases of post-partum necrosis Farquhar- made to assess two variables-the sensitiv'ity to son (I950) found that only seven weighed less than insulin and the response to the hypoglycaemia Ioo lb., five being described as' thin or emaciated.' which insulin produces. All cases should be on a He also stated: ' It would appear that complete high carbohydrate diet for four days previously. destruction of the gland is followed at once by loss After withdrawing blood for fasting blood sugar of weight and other symptoms of the disease.' It estimation, insulin is injected intravenously to seems probable that the apathy and loss of interest reduce the blood sugar level by at least 45 per cent. and of appetite found in the severe cases may lead Normally this may be achieved by a dose of o.I to considerable weight loss at various times in the units/kg.,'but in suspected panhypopituitarism not course of the illness. The case described by more than one-third of this dose should be given as Aitken and Russell (i934), in which the pituitary there may be great sensitivity to insulin. It is was destroyed by haemorrhage into a chromo- best to talk to the patient as clouding of conscious- phobe adenoma, lost 35 lb. in as many weeks after ness may be the first indication of dangerously low the haemorrhage, while the case of Farquharson blood sugar levels, in which case the test should be and Graham (193I), with post-partum necrosis, terminated with a glucose drink. Blood is taken gained 20 lb. when her appetite improved for some for glucose estimations at 20, 30, 45, 6o and- I20 years before death. A complication such as minutes after the injection. . Normally when the tuberculosis, which is not uncommon, may also blood sugar level has been halved the response is reduce the weight. rapid and the normal level is regained within two While post-partum necrosis of the gland is the hours. There may be considerable delay in commonest cause of pituitary failure in women, in myxoedema and in Addison's disease, but in men the syndrome results from fibrosis, granuloma severe hypopituitarism the response may be almost or tumour. The onset is gradual, usually with absent, and this feature, together with the greatby copyright. loss of libido and of potentia. The external sensitivity to insulin, is characteristic. genitalia and prostate become small and the voice The test should not be performed if the fasting may become high-pitched. The patient rarely blood sugar is much below normal as it may be in has to shave. cases of hyperpituitarism. A number of these patients become comatose, (3) Conadotropins. The urinary excretion of often with little warning. In many cases this is FSH is greatly reduced (Klinefelter, Albright and due to hypoglycaemia, which may occur even after Griswold, '943; Escamilla, 1949). The test is comparatively short periods of fasting or after the based on the original method of Zondek (I930), administration of insulin given to stimulate the depending on the enlargement of the uterus of http://pmj.bmj.com/ appetite or as a diagnostic measure. Other cases immature mice by extracts of tne urine injected are liable to crises similar to those of Addison's after serial dilution. Extracts can be prepared disease with diarrhoea, vomiting and collapse. either by alcohol precipitation or by ultra- Occasionally coma is associated with disturbances centrifugation. of body temperature, either with fever and tachy- (4) Robinson-Power-Kepler test. This empirical cardia at the onset of an infection, to which the test depends upon the summation of the anomalies patient may readily succumb, or, rarely, with of renal function found in adrenal deficiency. severe hypothermia. Sheehan and Summers These are: (a) Lowered renal blood flow on September 26, 2021 by guest. Protected (1952) have described one case in which the tem- and glomerular filtration rate with consequent perature had to be measured with a bacterio- lowered urea clearance and raised blood urea. In logical thermometer, being as low as 87° F. The panhypopituitarism this is partly due to the de- patient was pulseless and the heart beat slow and ficiency of growth hormone which is probably almost imperceptible. She was revived by im- responsible for the microsplanchnia. The average mersion in a warm bath. weight of the two kidneys in Sheehan and Sum- mers's cases was i70 g. (normal 300 g.); (b) Laboratory Investigations failure of water diuresis in response to a water (I) Urinary 17-ketosteroids. Fraser and Smith load, with nocturia. The cause of this is uncertain, (I941) found an excretion of less than 0.5 mg./24 hr. but appears to be due to loss of tubular selectivity, in nine of ten cases, the normal range in women for the patient being unable to pass large volumes of their laboratory being 5 to I5 mg./24 hr. Venning dilute urine, or small volumes of very concentrated and Browne (I949) and Escamilla (I949) reported, urine, in response to the appropriate stimuli. somewhat higher values, but in every case they Severe cases pass small volumes of urine with a Postgrad Med J: first published as 10.1136/pgmj.29.330.192 on 1 April 1953. Downloaded from April 1953 LEWIS: Hypopituitarism 195 chloride concentration similar to that ofthe plasma, cases have been recorded where quite a small sur- irrespective of hydration, or dehydration, during viving remnant of the gland has been found post- the day (Chalmers and Lewis, i95I). At night mortem and has evidently prevented the occurrence large volumes of less concentrated urine may be of any of the symptoms of the syndrome. This is passed (Robertson, I95Ia). analogous to the finding that only a small part of In this test a water load of 20 ml./kg. is given to the secreting tissue of the neurohypophysis may the fasting patient in the morning, after the night prevent the occurrence of diabetes insipidus. In urine specimen has been collected. Further some cases the complete syndrome of panhypo- specimens are collected at hourly intervals. In pituitarism may only develop after many years. the patient with adrenal deficiency none of these Hubble (i952) describes a case in -which the pubic specimens will be larger than that collected over- hair disappeared and amenorrhoea developed after night because of the nocturia and failure of diuresis a post-partum haemorrhage, but adrenal and in this condition, but this anomaly is not diag- thyroid failure were delayed for 25 years. This nostic. In the second part of the test the following emphasizes the importance of Sheehan and Sum- index is derived: mers's description of the complete syndrome, for they were careful to base this only on the study of Vol. of largest day urine Plasma chloride Urinary urea x X longstanding severe cases. Vol. of night urine Urinary chloride Blood urea In many other cases the pituitary failure may never be more than partial. Sheehan and Mur- In adrenal deficiency the factors ofthe numerator doch (1938) reviewed the histories of I28 women tend to be lower than in normals, while those of the who had suffered from post-partum haemorrhage denominator are greater, so that the figure de- and collapse between 1930 and i936. Absence of rived is a low one. Robertson, Power and Kepler any mammary reaction was the commonest sign of (I94I) found that the factor was below 25 in pituitary failure and occurred in 44 cases. Three adrenal deficiency and above 30 in normals, of these were in the group with the least degree cases with cachexia or with though occasionally of collapse and had no other symptoms. Men- by copyright. hepatic or renal failure gave anomalous results. struation was absent or infrequent in 32 cases, (5) B.M.R. This is abnormally low, usually while body hair was lost in only i . Failure of below -30. The serum cholesterol may be lactation and of sexual function are therefore the raised, but is not usually in the range found in commonest symptoms, but the second of these is primary myxoedema. not invariable. Several cases have been reported (6) Plasma electrolytes. The sodium and chlor- in which extensive destruction of the gland has ide levels may be low and that of potassium high, been found post-mortem, but menstruation and but the figures are often normal. even pregnancy had occurred after the onset of Response to the of ACTH. It may the disease. and de Mowbray have (7) injection Bishop (I95i) http://pmj.bmj.com/ take several injections of the hormone to elicit a described a patient who developed symptoms of full adrenal response, which may tnerefore be less hypopituitarism with almost complete amenor- at first than that found in normals but greater than rhoea after a pregnancy at the age of 22. She that in Addison's disease. It has been suggested twice became pregnant subsequently, going to (McIntosh et al., 1950) that this incomplete re- term on the second occasion and improving con- sponse may be valuable in diagnosis and that a siderably during this time, but relapsing after the clear distinction can be made between the rises in confinement.

17-ketosteroid excretion in patients with hypo- Oelbaum (1952a) emphasizes the variability of on September 26, 2021 by guest. Protected pituitarism and in normals after ACTH. However, endocrine dysfunction in post-partum hypo- this perhaps overestimates the significance of pituitarism. One case showed. only a deficiency of minor variations in the results of a complicated gonadotropin excretion; amenorrhoea was com- chemical analysis. plete, but thyroid and adrenocortical function were considered to be normal. The urinary I7 Incomplete Lesions ketosteroid excretion was 7.0 mg./24 hr., and the Detailed study of the patients suffering from insulin tolerance test normal. Another case had post-partum necrosis of the anterior lobe has led a normal gonadotropin excretion but was found to to an appreciation of the true nature of the syn- have an infantile uterus at a subsequent laparo- drome of hypopituitarism. Where haemorrhage tomy. Cooke and Sheehan tI950) stress that and collapse in the p erperium have been followed patients may suffer from genital superinvolution, by the appearance of less complete degrees of de- deficiency of thyroid or adrenal cortical function ficiency the definite time of onset fixed by the or hypoglycaemia or from any combination of clinical history has enabled the evolution of the these, and believe that the irregularities depeid on disease to be followed from the beginning. Several the amount of the pituitary destroyed and the Postgrad Med J: first published as 10.1136/pgmj.29.330.192 on 1 April 1953. Downloaded from i96 POSTGRADUATE MEDICAL JOURNAL April 1953 time which has elapsed since destruction. One of had had one child. Of 2,000 cells in the anterior their cases menstruated for six years before the pituitary only o.z per cent. were eosinophils. full syndrome developed. Another developed Occasionally cases occur with isolated de- amenorrhoea and genital atrophy after her only ficiencies of gonadotropic or of thyrotropic hor- pregnancy but breast-fed the baby for three months. mones (Hubble, 1952). Paschkis and Cantarow (I95 ) reported one case with normal 17-ketosteroid excretion but hypo- Hypopituitarism Secondary to Nutritional glycaemia unresponsiveness, and four with the and Psychogenic Factors converse. These results favour the hypothesis that In a recent stimulating review of the course of adrenal androgen production is controlled by the anterior hypopituitarism Hubble (I952) has dis- secretion of LH rather than the suggestion, made cussed the failure of sexual function and growth by the authors, that the adrenal functions may be that may occur in such conditions as anorexia individually suppressed. nervosa and coeliac disease. While amenorrhoea In 1940 Means, Hertz and Lerman described in anorexia nervosa is frequently psychogenic, the syndrome of' pituitary myxoedema.' This is there is reason to believe that in some cases it is essentially a condition of hypopituitarism in which due to the malnutrition. It is known that in rats the predominant features are those of thyroid a deficient diet may depress sexual function before deficiency. Unless carefully sought, signs of de- restricting growth. Banks, Lloyd and Scowen ficiency of other pituitary hormones may not be (I952) reported that severe diet restriction in two found and the case may be mistaken for one of women after the menopause reduced the excretion primary myxoedema. It must be borne in mind of FSH to zero in a few weeks. There is usually that while hypopituitarism frequently occurs no other evidence of pituitary deficiency in without much loss of weight, any such loss in the anorexia nervosa, though the B.M.R. is usually course of the disease is strongly against the diag- low. Thorn et al. (I950) observed a low 17- nosis of primary myxoedema. It is important to ketosteroid excretion and considered that this was recognize such cases because they may react in an evidence of impaired adrenal function, but other anomalous manner to thyroid. Occasionally small laboratory investigations such as the insulin by copyright. doses may precipitate an adrenal crisis, presum- tolerance test and the Robinson-Power-Kepler ably by suddenly increasing the demand for test are normal. adrenal hormones. On the other hand some cases Dwarfism is usual when coeliac disease per- are resistant to thyroid and show little improve- sists into adult life, in fact, if skeletal develop- ment with doses effective in primary myxoedema. ment is retarded by more than a few years it Chromophobe adenomata frequently cause pro- usually persists, at least partially, even when the gressive hypopituitarism. Here again in the great nutritional deficiencies are completely corrected. majority of cases sexual failure occurs first. One of Hubble's cases was still growing in his Amenorrhoea occurs in women, without meno- thirties, so that production of sex hormones (which http://pmj.bmj.com/ pausal symptoms, and in men there is loss of ultimately limit growth by causing fusion of the libido and potentia. Dott, Bailey and Cushing epiphyses) was evidently more depressed than that (I925) emphasized the importance of these symp- of growth hormone. toms early in the course of pituitary destruction by chromophobe tumours. In many cases there is Differential Diagnosis little evidence of other deficiencies for many years, Anorexia nervosa. This is the condition which is and it is for of the sella and most possible enlargement frequently mistaken for Simmonds' disease, on September 26, 2021 by guest. Protected optic atrophy to occur with normal pituitary and there is no doubt that descriptions of the latter function. in the past have been vitiated by reports of cases in which these two conditions have been confused. Pituitary Dwarfism The patient with anorexia nervosa in an advanced In this condition, hypopituitarism in childhood stage is emaciated, but in spite of this her mental manifests itself mainly in failure of growth. The and physical activity is often quite remarkable, child is small but normally proportioned. Usually whereas in panhypopituitarism the patient is dull, sexual maturation never occurs so that a very slow apathetic and inert even when the weight is normal. rate of growth may be maintained for many years. In anorexia nervosa amenorrhoea occurs early but The signs of thyroid and adrenal deficiency are not body hair is not lost. Apart from a low B.M.R. usually evident. Sometimes the cause is a the other laboratory investigations are generally pituitary tumour such as a craniopharyngioma. In normal. other cases there appears to be an isolated de- Addison's disease. Body hair is often absent and ficiency of growth hormone production. Hewer the urinary excretion of I7-ketosteroids is low in (I944) reported the necropsy of a female dwarf who women with Addison's disease, presumably be- Postgrad Med J: first published as 10.1136/pgmj.29.330.192 on 1 April 1953. Downloaded from April 1953 LEWIS: Hypopituitarism I97 cause of the failure of production of adrenal Treatment androgens, but in hypopituitarism the character- Sheehan and Murdoch (I938) reported a case istic pigmentation of Addison's disease is not in which improvement occurred during pregnancy seen and low blood pressure with low serum levels following previous post-partum necrosis, and it of sodium and chloride and high potassium occur was thought that some hyperplasia of the remnant much less often. As Thorn et al. (Ix949) have of the anterior lobe had occurred. The case of pointed out, the adrenal deficiency of hypo- Bishop and de Mowbray improved in pregnancy pituitarism appears to lead predominantly, to but relapsed later. The patients reported by hypoglycaemia rather than to hypochloraemia. In Jakob (1923) and Farquharson, Belt and Duff the insulin tolerance test the patient with Ad- (I938) became worse after pregnancy. It appears, dison's disease may be less rather than more therefore, that the chances of any real improve- sensitive to insulin than normal (possibly because ment occurring as the result of pregnancy, even in. of increased glycotropic activity of the anterior the unlikely event of conception taking place after pituitary), though there is hypoglycaemia un- post-partum necrosis, are extremely small. responsiveness (Fraser, Albright and Smith, Pituitary failure is not an indication for surgery I94'). in cases with cysts or tumours in the neighbour- Myxoedema. The importance of distinguish- hood of the sella; in the great majority of cases ing between primary myxoedema and so-called surgery is undertaken to save the sight. Opera- pituitary myxoedema has been emphasized above. tion may, in fact, abolish what little endocrine While the latter type rarely occurs without sexual function remains, with a fatal outcome (Grant, failure, as Hubble has stressed, reports in the 1948). Caughey, James and Macleod (I952) re- literature of cases in yvhich menstruation and preg- ported four cases in which prolonged stupor de- nancy have occurred in undoubted hypopituitarism. veloped after operations on pituitary tumours. do not make even this distinction completely re- Recovery occurred in two on treatment with liable. In primary myxoedema urinary I7- cortisone. ketosteroid excretion may be very low and the by copyright. blood sugar may n6t return to normal in the in- In the great majority of cases the only possible sulin tolerance test. A distinction between these treatment is some form of hormonal replacement two conditions may therefore be very difficult to therapy. A course of ACTH (25 mg. intra- make. A detailed inquiry into the sexual function, muscularly, six-hourly for a few days) brings about menstrual rhythm and obstetric history, careful a dramatic improvement in those cases with symp- examination of the fundi and of the visual fields, toms of adrenal deficiency. Increased appetite, radiological examination of the pituitary fossa and activity and libido, and euphoria and gain of investigation of adrenal function may therefore be weight occur, and this improvement may last for in a doubtful case. The weeks after the end of the course (Rolland and necessary difficulty of http://pmj.bmj.com/ making this distinction again emphasizes the im- Matthews, 1952; Summers and Sheehan, I951; portance of starting thyroid therapy with small Hart, 195I). A normal diuretic response to water doses of the hormone and the dangers of giving may be obtained (Chalmers and Lewis, I95i), and thyroid indiscriminately to any patient. the nocturia may lessen. Hypoglycaemia may be Primary ovarian insufficiency (Albright, Smith prevented. Cortisone (25 mg. a day by mouth) and Fraser, 1942). This is sometimes mistaken brings about a similar improvement and is the best for There be maintenance therapy. Either ACTH or cortisone hypopituitarism. may other stigmata should be whenever becomes neces- such as webbing of the neck, coarctation of the given surgery on September 26, 2021 by guest. Protected aorta or cubitus valgus. Body hair is scanty but sary. Treatment of the adrenal deficiency with not absent, and the breasts are small. Sexual DOCA and extra salt give much less dramatic functions have never matured and the body pro- results than in cases of Addison's disease, though portions are eunuchoid, the span being greater than it may be beneficial. the height. These patients are not dwarfs but are Thyroid should only be given with extreme usually moderately stunted, the height often being caution, starting with ~ gr. daily while the patient about 4 ft. 8 in. Assay of the urinary FSH ex- is under observation. The simultaneous ad- cretion clinches the diagnosis for it is high in this ministration of ACTH, DOCA or extra salt condition. reduce the risk of precipitating an adrenal crisis. Other mistaken diagnoses, commonly made on In some cases the dose of thyroid can be greatly account of the appearance, are those of anaemia or increased and the effects may be striking, par- nephritis, the latter particularly when nocturia is a ticularly on the lethargy and the mental changes. prominent symptom. 'Post-partum debility,' Injections of growth hormone are ineffective in neurosis and various psychoses may also be pituitary dwarfism. Growth may be stimulated diagnosed. by androgen therapy but will cease when this Postgrad Med J: first published as 10.1136/pgmj.29.330.192 on 1 April 1953. Downloaded from i98 POSTGRADUATE MEDICAL JOURNAL' April I953 brings about fusion of the epiphyses; 5oo-I0ooo and cortical extract (preferably lipo-adrenal i.u. of chorionic gonadotropin twice a week.may cortex if this is available, as this contains more stimulate growth and sexual function in these glucocorticoid fraction). DOCA (5 or Io mg.) cases. should be injected intramuscularly at the same Adult females with hypogonadism can be given time, and as infection is so frequently the cause of oestrogens with benefit. the collapse, a large intramuscular dose of peni- In all cases testosterone therapy is beneficial, cillin or intravenous aureomycin should be often strikingly so. In addition to stimulating a given. sense of wellbeing and libido, it brings about in- The treatment of pituitary coma has recently creased protein anabolism with a positive nitrogen been fully discussed by Sheehan and Summers balance and weight gain in both sexes. Muscular (1952). They observed no improvement following development and vigour increase and, in males, intravenous cortisone, saline or DOCA. They the penis enlarges and erections become frequent. emphasized the importance of recognizing hypo- It is claimed that spermatogenesis may be stimu- thermic coma. This occurred in one of their lated (Hurxthal, Bruns and Musulin, I949). patients in spite of previous injections of DOCA, Body hair is increased. These actions have been recovery occurred after immersion in a warm bath. discussed by Oelbaum (I952b). Methyl testo- One of the dangers of hypopituitarism lies in sterone can be given sublingually, testosterone pro- the fact that the patient may be so apathetic that pionate can be given by injection or, most con- she fails to realize when her condition has de- veniently, 200 mg. of testosterone can be im- teriorated and a doctor may not be called until a planted. crisis or coma has developed. Death may follow Crisis and coma call for immediate and vigorous with appalling suddenness in. such cases in spite treatment. As hypoglycaemia is the commonest of all efforts on the part of the physician. The single cause large quantities of glucose must be prognosis in any severe case of hypopituitarism is given by mouth or intravenously. ACTH and therefore always grave and never exactly pre-

cortisone can be given simultaneously but their dictable. The patient must be kept under regularby copyright. effect will not be felt for some hours, so that observation and must be told to report at once if diarrhoea and vomiting call for intravenous saline any infection develops.

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