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HYPOPITUITARISM by A 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.
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