Fuller Albright

STUDIES ON THE PHYSIOLOGY OF THE PARATHYROID GLANDS: I. Calcium and Phosphorus Studies on a Case of Idiopathic Hypoparathyroidism

In order to determine, if possible, the exact train of events which lead to a rise in the serum calcium following the injection of a potent parathyroid extract, we undertook the present series of investigations. The subject of this study was an Italian boy on whom the diagnosis of idiopathic hypoparathyroidism was made. The criteria on which such a diagnosis can be based will be discussed below. The injection of a potent parathyroid extract results in four wellestablished changes and any theory as to the action of a parathyroid extract will have to take cognizance of these four cardinal points. They are: a. Rise in serum calcium (1). b. Rise in urinary calcium excretion (2) (3) (4). c. Fall in serum phosphorus (5). d. Rise in urinary phosphorus excretion (2) (3). Removal of the parathyroid glands results in the converse changes, i.e., a. Fall in the serum calcium. b. Fall in the urinary calcium excretion. c. Rise in the serum phosphorus. d. Fall in urinary phosphorus excretion. In addition Albright, Bauer, Ropes, and Aub (3) emphasize the fact that on administration of parathormone, the increase in urinary phosphorus excretion tends to precede the increase in calcium excretion. They further point out that the increased phosphorus appearing in

STUDIES OF CALCIUM AND PHOSPHORUS METABOLISM: IV. The Effect of the Parathyroid Hormone

In the course of our studies in calciulm metabolism evidence has steadily accumulated that the metabolism of acid-producing substances plays an important r6le in influencing the assimilation and excretion of calcium. This effect, however, has not been adequately studied in man, and in other studies of calcium exchange the potential acidity or alkalinity of foods and medication has largely been neglected. It is the purpose of the present investigation to follow the effect of food-stuffs and inorganic salts on calcium metabolism with relation to their potential acidity (after oxidation) referred to the hydrogen ion concentration of the blood. Studies in rickets for some time have indicated the importance of acidity to the assimilation and storage of inorganic salts in bone. Thus, McClendon (1) noted that the addition of alkali to a diet increased its power to produce rickets and, conversely, Zucker, Johnson, and Barnett (2) reported that the change in acidity of diets from the alkaline toward the acid side of neutrality might result in healing of the rachitic lesions. Much work, too, has been done upon the effect of administered acid on the mineral excretion. The experiments of Givens and Mendel (3) and of Givens (4) upon the effect of base and acid on the general metabolism tended to minimize variations in calcium excretion resulting from this factor. Subsequently, Goto (5), using rabbits, demonstrated depletion of the skeleton by repeated doses of hydrochloric acid. Lamb and Evvard (6) demonstrated increased urinary calcium

STUDIES IN PARATHYROID PHYSIOLOGY: III. The Effect of Phosphate Ingestion in Clinical Hyperparathyroidism

In the second paper of this series (1) the disorders of calcium phosphate metabolism were divided into three fundamental groups. It was believed that under normal conditions body fluids contain all the calcium phosphate which that particular fluid system can hold at that particular time. The first and commonest group was that in which the body fluids contain less than this saturating amount of calcium phosphate. Because of this, calcium phosphate is not deposited into osteoid tissue with the resulting pathological picture of wide osteoid seams on the trabeculae (cf. rickets and osteomalacia). The second group was that in which the body fluids, because of certain extraordinary circumstances, contain more than the normal quota of calcium phosphate and deposition in tissues other than osteoid tissue results (e.g. ergosterol poisoning and cases of metastatic malignancy and myeloma). Finally, a third possibility presented itself. It is conceivable that the body fluids might contain a normal saturating amount of calcium phosphate, but that the proportion of the calcium ions to the phosphate ions might be abnormal. Such, it was believed, is the disorder in diseases of the parathyroid glands. To recapitulate then, we conceived of three possible variations from the normal saturation of body fluids with calcium phosphate: (a) subsaturation, (b) supersaturation, and (c) anomalous-saturation (i.e. quantitatively normally but qualitatively abnormally saturated). In the first paper of this series (2), the hypothesis was advanced that this abnormality in the relation of the calcium ion to the phosphate ion in parathyroid disorders was dependent upon changes in phosphorus excretion in the urine brought about by the parathyroid hormone. Thus it was believed that on administration of the parathyroid hormone the first effect was an increased phosphorus excretion; that this resulted in a decreased serum inorganic phosphorus; that this tended to leave the serums capacity to take up calcium phosphate unfulfilled; that calcium

PARATHYROID HYPERPLASIA IN RABBITS PRODUCED BY PARENTERAL PHOSPHATE ADMINISTRATION

Frolmi the observations of Bergstrand (1) and others (2, 3, 4) it has become an established fact that some cases of chronic renal insufficiency are accompanied by enlargement of the parathyroid glands. The condition was well exemplified by a case recently studied at the Massachusetts General Hospital in which chronic glomerular nephritis had existed for more than twenty years, and in which necropsy revealed tremendous enlargement of all parathyroid glands (5). The question as to the cause of the parathyroid enlargement arises. It was suggested by Albright, Baird, Cope and Bloomberg (6) that the phosphate retention in chronic renal insufficiency might be the determining factor. When the blood phosphate level is raised by intravenous phosphate administration, hypocalcemia and tetany ensue (7). It seemed not unlikely that either hyperphosphatemia or the resulting hypocalcemia might be a stimulus to parathyroid hyperplasia. The present investigations were undertaken to determine the effect of administration of parenteral phosphate on the parathyroid glands of rabbits.

STUDIES OF CALCIUM AND PHOSPHORUS METABOLISM: VI. In Hypoparathyroidism and Chronic Steatorrhea with Tetany with Special Consideration of the Therapeutic Effect of Thyroid

Following the observation by Aub, Bauer, Heath, and Ropes (1), that the thyroid hormone exerts a marked effect upon the excretion of calcium, it became of interest to determine the therapeutic effect of this internal secretion upon the calcium metabolism in tetany. In hyperthyroidism, although the blood calcium and phosphorus levels are essentially normal, the calcium and phosphorus excretions are abnormally high. Tetany of the low calcium variety, however, has been shown to have an abnormally low calcium excretion associated with the abnormally low blood calcium level. The primary purpose of these metabolic studies was to study the influence of thyroid medication on the level of calcium and phosphorus in the blood and excreta of patients suffering from tetany. Other observations, however, were made for comparison and this paper includes data illustrating the influence on inorganic salt metabolism of:

THE LOCUS OF ACTION OF THE PARATHYROID HORMONE: EXPERIMENTAL STUDIES WITH PARATHYROID EXTRACT ON NORMAL AND NEPHRECTOMIZED RATS

The administration of parathyroid extract causes well-known changes in the calcium and phosphorus metabolisms. Albright and Ellsworth (1) advanced the theory that the changes in the calcium metabolism, including changes in bone, were dependent upon preceding changes in the phosphorus metabolism; they, furthermore, believed that the lowering of the serum phosphorus level was the result of an increased phosphate excretion in the urine. Collip, Pugsley, Selye, and Thomson (2), however, after a study of the long bones of 8 nephrectomized rats that had been injected with parathyroid extract, concluded that the action of the parathyroid hormone on bone tissue is not dependent upon a preceding phosphorus diuresis. Likewise, McJunkin, Tweedy, and McNamara (3) found that the administration of large doses of parathyroid extract to nephrectomized rats produced a pronounced resorption of bone although it did not produce a characteristic rise in serum calcium. In spite of these studies, there still seemed room for doubt: Collip, et al. did not publish results with nephrectomized controls, and the possibility existed that nephrectomy alone, with its concomitant acidosis, might lead to bone resorption; McJunkin, et al. did publish results on nephrectomized controls, but their control animals were considerably heavier and presumably older than the experimental animals (control animals, 151 grams, as compared with experimental animals, 110 grams, average per animal). The studies here to be reported are a repetition and an extension of the above observations, with certain modifications and different methods, to determine whether the above results could pos-

The cardiac output in paget's disease before and after treatment with cortisone

Abstract 1.1. Observations on the cardiac output have been made in six patients with extensive Pagets disease before and during treatment with large doses of cortisone. 2.2. In all cases, cardiac output was elevated before treatment. High doses of cortisone for a sufficient duration, more than three days and less than nine days, produced a pronounced fall to normal levels. Serum alkaline phosphatase levels changed in the same direction as the cardiac output. 3.3. Cortisone had no consistent effect on oxygen consumption, large vessel hematocrit, total blood volume, pulse pressure or mean arterial pressure. Cortisone therapy resulted in a pronounced drop in pulse rate in three of the six patients studied. 4.4. The mechanism through which cortisone exerts its effect on cardiac output in Pagets disease was not elucidated by these studies.

A COMPARISON OF THE EFFECTS OF VITAMIN D, DIHYDRO-TACHYSTEROL (A.T. 10), AND PARATHYROID EXTRACT ON THE DISORDERED METABOLISM OF RICKETS

In a previous paper (1) it was concluded that vitamin D has two fundamental and separate actions: (a) to increase the absorption of calcium from the gastro-intestinal tract, and (b) to increase the phosphate excretion in the urine. In a later paper (2) evidence was brought forth which suggested that A.T. 10 (dihydrotachysterol) has both these properties but that the ratio of the calcium absorption factor to the phosphate excretion factor is less with A.T. 10 than with vitamin D. It was pointed out (2), furthermore, that the effect of either A.T. 10 or vitamin D on phosphate excretion may be masked in patients with their parathyroids intact by a tendency in the opposite direction resulting from decreased parathyroid activity occasioned by the increased calcium absorption. It was thought that the reason A.T. 10 was not antirachitic was because of this increased effect on phosphate excretion, a property obviously not antirachitic. Finally, it was pointed out (2) that the parathyroid hormone differed in action from both vitamin D and A.T. 10 in having only the effect on phosphate excretion in the urine without any effect on calcium absorption. It was decided to test the above conclusions by studies on a patient with chronic infantile rickets. The subject of the investigation was a boy of 17 with vitamin D resistant rickets. He was the same boy who was previously reported (3) on whom it was shown that the disordered metabolism was essentially the same as in the usual form of rickets but to whom it was necessary to give massive doses of vitamin D before therapeutic results were obtained. In the present investigation the metabolic effects of A.T. 10 and parathyroid extract were studied. These data can be compared with those from similar studies already reported with vitamin D on the same patients (3). Whereas these latter studies were conducted approximately 5 years before, the underlying metabolic disorder was essentially the same during both studies. To be sure, the bones were much less rachitic during the present investigation. On the other hand the blood valuesserum calcium, phosphorus, and phosphatasewere almost identical at the beginning of both investigations.

The Classic: The Metabolic Effects of Steroid Hormones in Osteoporosis

This Classic Article is a reprint of the original work by E.C. Reifenstein Jr. and F. Albright, The Metabolic Effects of Steroid Hormones in Osteoporosis. An accompanying biographical sketch of F. Albright is available at DOI 10.1007/s11999-011-1831-0. The Classic Article is ©1946 and is reprinted with permission from The American Society for Clinical Investigation from Reifenstein EC, Albright F. The metabolic effects of steroid hormones in osteoporosis. J Clin Invest. 1947;26:24–56.