The Effect of Adrenocorticotropic Hormone in Panhypopituitarism 1

A priori one would anticipate that the effects of a hormone would be most apparent when given to an individual lacking that hormone.To be sure, when the hormone acts through another gland, as does adrenocorticotropic hormone (ACTH), one might find the "target" gland unresponsive through atrophy.In panhypopituitarism, one is dealing not with a single deficiency, but with a deficiency of all "tropic" hormones.This may be advan- tageous for the study of any one of them, in that compensatory changes in the others cannot obscure the results.It may be disadvantageous in that some of the effects might not occur in the face of other deficiencies.All in all, we decided to employ three patients with panhypopituitarism 4 for our first studies of the metabolic effects of ACTH.Preliminary re- ports of this work have appeared (1, 2).A num- ber of other reports of the metabolic effects of ACTH are now available (3-9).CASE SUMMARIES (1) Patient M.W., female aged 43, M.G.H. No. 160,451, had a severe postpartum haemorrhage 17 years before the study.After delivery she did not lactate and her periods did not return.She remained weak and had an anemia resistant to iron treatment.On six subse- 1 The expense of these studies was partly defrayed by grants from the Rockefeller Foundation, the National Advisory Cancer Council, Ayerst, McKenna and Harri- son, Ltd., and the American Cancer Society on the recom- mendation of the Committee on Growth of the National Research Council.A bed supported by Mr. Edward Mallinckrodt on the Metabolic Ward was used for these studies.5 Method of Talbot and his associates (10).The test depends on the reduction of alkaline copper tartrate.Normal subjects excrete between 0.10 and 0.44 mg. per 24 hours (11).B By "cortin" we mean urinary corticoids assayed biologically (12).The test depends on the amount of glycogen formed in the livers of fasting, adrenalectomized mice.Normal subjects excrete more than 3 and less than 24 mouse units per 24 hours. EFFECT OF ACTH IN PANHYPOPITUITARISMvalues were obtained: sodium 146 m.eq./L; chloride 103 m.eq./L; potassium 4.8 m.eq./L; carbon dioxide content 32 m.eq./L; glucose 93 mg. per 100 ml.; non-protein nitrogen 25 mg.per 100 ml.; total protein 7.0 gm. per 100 ml.; calcium 9.5 mg. per 100 ml.; inorganic phosphorus 4.3 mg. per 100 ml.; alkaline phosphatase 2.7 Bodansky units; cholesterol 284 mg. per 100 ml.; pro- tein bound iodine 3.5 micrograms per 100 ml.The hemo- globin was 12.4 gm. per 100 ml.Twenty-four hour urine specimens contained 1.7 mg. of 17-ketosteroids, more than 3 but less than 6.5 mouse units of follicle stimulating hormone, 0.1 mg. of "11-oxysteroids" and less than 1.5 mouse units of "cortin."Two insulin tolerance tests showed hypoglycemia unresponsiveness.A testicular biopsy was interpreted by Dr. Ronald S. Sniffen as follows: "The testis has tubules in all stages of activity from normal to those lined solely by a thickened tunica propria which is peppered with granules.The Leydig cells are present in normal num- bers; most of them are solid, but a few contain vacuoles, crystalloids or pigment."Following unsuccessful X-ray therapy, a chromophobe adenoma was partially removed by trans-sphenoidal ap- proach.The first metabolic study preceded, the second and third followed this operation.(3) Patient M.H., female aged 56, M.G.H. No. 568,954, complained of loss of energy for five years, dry hair for four years, cold sensitivity for two years, and episodes of weakness or dizziness, occurring in mid-morning, for one year.Menses had ceased 13 years previously without hot flashes.She showed the facies of myxedema, dry thin skin, absent axillary and scant pubic and eyebrow hair, a slightly enlarged tongue, a very small thyroid, and a blood pressure of 190/95.X-rays revealed a normal sella turcica.The basal meta- bolic rate was minus 37.The following serum values were obtained: sodium 108 m.eq./L; chloride 82 m.eq./L; potassium 5.7 m.eq./L; carbon dioxide content 27.2 m.eq./L; glucose 116 mg. per 100 ml.; non-protein nitro- gen 24 mg.per 100 ml.; total protein 8.2 gm. per 100 ml.; calcium 9.1 mg. per 100 ml.; inorganic phosphorus 3.5 mg. per 100 ml.; alkaline phosphatase 3.5 Bodansky units; cholesterol 451 mg. per 100 ml.; protein bound iodine 1.0 microgram per 100 ml.The hemoglobin was 9.4 gm. per 100 ml.Twenty-four hour urine specimens contained 1.0 mg. of 17-ketosteroids, more than 6.5 but less than 13 mouse units of follicle stimulating hormone (very low for the post-menopausal state).Two insulin tolerance tests showed hypoglycemia unresponsiveness.A Kepler water test gave an abnormal result and the calculated "index," A, was 19.PROCEDURE Five balance studies (13) were carried out.In these the effects of ACTH (Armour 7) were observed and 7 We wish to express our gratitude for the generous grants of ACTH made available to us by Dr. John Mote of Armour and Company.We are indebted to Dr. TABLE I Sequence, duration, and dosage of treatments in five balance studies 2 (an.1947)