Diabetes Insipidus Secondary to Penetrating Thoracic Trauma GEORGE MACHIEDO, M.D., PAUL J. P. BOLANOWSKI, M.D., JAMES BAUER, M.D., WILLIAM E. NEVILLE, M.D.
Three cases of diabetes insipidus following non-cranial trauma are presented. They are believed to be the first of their kind reported. The etiology, pathogenesis and differential diagnosis of diabetes insipidus are discussed. The literature if briefly reviewed and similarities between patients with DI due to long bone trauma with fat embolism, post open heart surgery hypotension, Sheehan's syndrome following postpartum hemorrhage, DI and our own patients are discussed. It is concluded that the diabetes insipidus is caused by selective disruption of posterior pituitary circulation due to fat globules, thrombi and hypovolemia resulting in hypoxia and tissue necrosis.
D IABETES Insipidus is an uncommon disease entity characterized by polyuria and polydysia. It arises
from one of several causes and can be classified as either primary or secondary.8 The primary causes are either idiopathic or familial. The secondary group consists mainly of pituitary tumors usually a chromaphobe adenoma, or other neoplasm near the pituitary or hypothalamic regions. In addition, secondary diabetes insipidus can result from granulomata involving the pituitary and trauma to that area. The latter usually consists of direct head injury with disruption of the hypothalmic-posterior pituitary axis. Recently we have seen three patients with post traumatic diabetes insipidus secondary to penetrating chest trauma unassociated with head injury. A thorough search of the English literature revealed only four documented patients with diabetes insipidus which even remotely resemble the three cases presented herein.267 Case Reports Case 1. A 17-year-old black male was admitted to the Martland Hospital on October 22, 1972 with a stab wound in the precordial area. The vital signs were absent and the pupils were dilated. He was intubated, ventilated and the fluid volume replaced with crystalloid solution and later type specific cross matched blood. He was immediately taken to the operating room where a 2 cm laceration at the apex of the right ventricle was closed. Following this, restoration of cardiac action was obtained and the blood pressure restored to normal. Postoperatively he had spontaneous respirations and his previously fixed, dilated pupils were smaller and Submitted for publication May 1, 1974.
From the New Jersey Medical School At Newark, Newark, New Jersey reacted to light. However he remained comatose and generalized convulsions supervened. These were controlled with diphenylhydantoin, phenobarbital, curare, and moderate external hypothermia. Five mgm of dexamethasone sodium phosphate were given every four hours to reduce cerebral edema. On the sixth postoperative day, he began excreting large amounts of diluted urine with a specific gravity of 1.005 without abnormal substances such as glucose or protein. A tentative diagnosis of diabetes insipidus was made which was further substantiated by administration of 10 units of intramuscuilar aqueouis pitressin. This reduced his hourly urine output from in excess of 400 ml/hour to less than 100 ml/hour. He was maintained on pitressin until he expired five days after the onset of diabetes insipidtis. During this time his rectal temperature ranged 33-37 C. Postmortem examination disclosed coagulation necrosis of the anterior pituitary with mild acute inflammatory infiltration. A large thrombus was noted in the vein surrounding the pituitary capsule with the capsular tissue also showing acute inflammatory changes (Fig. 1). The posterior pituitarv presented hemorrhage andacute and chronic inflammatory infiltrates (Fig. 2). There was widespread necrosis of neurons which was more marked in the cortex than in the pons. The outer zones of the cortex showed acute inflammatory infiltrates which were mainly perivascular. Fibrin thrombi were noted in the meningeal vessels. The right kidney was congested and multiple small fibrin thrombi were noted in the outer cortex that were not related to glomeruli. Acute tubular necrosis was not observed. Case 2. J.C., a 15-year-old black male was admitted to the Martland Hospital August 23, 1972 in severe respiratory distress from a gunshot wound of the right chest. Following intraveneous Ringer's Lactate his arterial blood pressure rose from 60/0 to 100/20. Because of marked neck vein distention and drainage of only 15 cc of blood following an insertion of a chest tube, he was immediately taken to the operating room where a right thoracotomy revealed cardiac tamponade, a 2 cm hole in the right atrium and a laceration of the right lung. Theseiwere repaired and the patient sent to the surgical intensive care unit with an arterial blood pressure of 110/70. However, he was non responsive and the pupils were fixed and dilated. The next 12 hours his urinary excretion averaged 425 ml/hour, at one point increasing to 1100 ml/hour for two hours. A tentatiye diagnosis of posttraumatic diabetes insipidus was made and 10 units of aqueous pitressin were given intramuscular. This reduced the urine output to about 150 cc/hour for the next five or six hours. His BUN at this time was 12 mgm% and the serum sodium was 146 mEq/L. The urine output again began to rise and the following day it was averaging 310 ml/hour. His serum osmolality was 336 mOsm/L and the urine osmolality was 64 mOsm/L. Specific gravity of the tirine was 1.001 and there was no glucose or acetone
MACHIEDO AND OTHERS
Fic. 1. Section of pituitary capsule demonstrating a large thrombus in vein. There is also noted an acute in flammatory infiltrate in the capsular tissues.
present. Following another injection of 10 units of pitressin the urine out put averaged 50 ml/hour, serum osmolality was 357 and the urine osmolality was 212. The following day without additional pitressin the serum osmolality was 361, the urine osmolality 402 with a urine output averaging 50 ml/hour. His rectal temperature ranged 33-37.5 C until he expired on the fourth postoperative day. Unfortunately the pituitary was not obtained at postmortem. However, sections taken from the cerebral cortex revealed no histologic changes. The kidneys did not show acute tubular necrosis. Case 3. An 18-year-old female entered the Martland Hospital Emergency Room on January 9, 1973 with a stab wound of the left infraclavicular region at the outer third of the clavicle. The blood pressure and pulse were uinobtainable and the patient was agonal with dilated but reactive pupils. Resuscitative measures included intubation, rapid infusion of 6 L of Ringer's Lactate followed by 6 units of blood. An immediate left anterior thoracotomy was performed in the emergency room with cardiac massage and ligation of the transected axillary artery. The vital signs returned and the patient was taken to the operating room where the partially transected axillary vein was repaired along with a laceration of the left lung, and the axillary artery. Postoperatively the blood pressure was 120/60, the pulse was 120, the CVP cm H20 and the urine output was 90 cc/hour. The patient remained unconsciouis but stable. On the fifth postoperative day the patient has a respiratory arrest but was immediately resuscitated. Following this the urine outpuit increased to an average of 550 ml/hour, and the diagnosis of diabetes insipidus was made. The serum osmolality was 329 with a urine osmolality of 92. Pitressin was given which increased the urine osmolality to 363. The urine output then averaged 250 ml/hour. On the sixth post-operative day the patient had a second cardiac arrest and expired. Postmortem examination of the anterior pituitary revealed coagulation necrosis with multiple foci of hemorrhage (Fig. 3). Recent thrombi were noted in the parietal venous vessels. The posterior pituitary showed small focal hemorrhage and edema. The cerebral cortex had focal hemorrhagic infarcts with subcortical white matter hemorrhage. Anoxic neuronal changes were noted in the substantia nigra but these were not associated with hemorrhage. The kidneys were congested but there was no evidence of acute tubuilar necrosis.
Discussion Regardless of its etiology the primary pathogenetic factor in true diabetes insipidus is a lack of circulating anti-
Stirg. jantiary 1975 -
diuretic hormone (ADH). This hormone is an octapeptide manufactured in the superoptic nuclei and paraventricular of the hypothalamus and transported along the hypothalamic posterior pituitary axis to be stored in the gland. It is normally released from the gland upon one or both of two stimuli. The first is a variation in the extracelluilar fluid volume (ECF). As the ECT is decreased, there is a concomitant increase of ADH released. This mediated through volume receptors located in the left atrium of the heart and in the aortic arch or carotid artery. The second stimuluis to release of ADH is an increase of plasma osmolality mediated through osmoreceptors in the internal carotid artery. After ADH is released from the posterior pituitary, it exerts its action directly on the kidney. The cite of action in the kidney is believed to be primary in the distal loop of Henle, the distal convoluted tubule and the collectint duct system. The hormone acts by making the cells of the distal nephron in the collecting duct more permeable to the passage of water, thereby allowing the normal hypertonic interstitium of the renal medulla to exert its osmotic effect on the hypotonic content of the tubles, that is, the urine. This draws water from the urine and makes it hypertonic in relation to the plasma allowing metabolities to be excreted without dehydrating the patient. The exact mechanism by which ADH exerts its effect on tubuilar cells is not well delineated although currently it is believed that like many other hormonal systems it is mediated by cyclic 3' to 5' AMP. Panhypopituitarism was first described by Simmons in 1914.12 He believed that the disease was caused by septic emboli resulting in infarct necrosis of the adenohypophysis. In 1938 Sheehan and Murdock10 described a syndrome of postpartum pituitary necrosis in patients who were in shock
Fic. 2. Section of posterior pituitary showing
hemorrhage, and acute and
chronic inflammatory infiltrate.
FIG. 3. Section of posterior pituitary showing hemorrhage, and
chronic inflammatory infiltrate.
from hemorrhage after parturition. They noted that the circulation to the anterior pituitary was decreased at normal delivery and postulated if a circulatory collapse were to occur the diminished blood flow would result in vascular thrombosis in the gland. In 1961 Sheehan and Stanfield"' claimed that the primary vascular disturbance during severe hemorrhage was arterial spasm with subsequent vascular thrombosis. They believed that the degree and severity of anterior pituitary necrosis was related to the duration and severity of the occlusive process. Later Sheehand and Whitehead9 even extended this theory to encompass posterior necrosis in order to explain the occurrence of diabetes insipidus. Another hypothesis to explain the pathophysiology of the pituitary insufficiency during pregnancy was advanced in 1962 by Beernink and McKay.' They showed that thrombosis, hemorrhage and necrosis of the hypothalamus, pituitary stalk and both lobes of the pituitary occurred in the presence of disseminated intravascular coagulation (DIC). Since ADH or its precursor is formed in the supraoptic and paraventricular nuclei in the hypothalamus and is carried along the tracks of the pituitary stalk to be stored in the posterior lobe of the pituitary, damage to any of these areas can result in diabetes insipidus. When secondary to trauma diabetes insipidus is usually due to closed head injuries in which the hypothalamic posterior pituitary transport mechanism is affected when the stalk is disrupted by shearing forces. The blood supply to the posterior pituitary usually remains intact since it is derived directly from the inferior hypophyseal artery. However, the neuronal paths along the neurosecretory granules travel are interrupted, thereby cutting off flow of the hormone to the pituitary making its release impossible. Since there was no evidence of a head injury in our
33 patients, it is possible that the polyuria could have been due to iatrogenic fluid overloading. However, in this instance, hyponatremia and a low serum osmolality should be evident. By contrast the patient with diabetes insipidus is dehydrated from his polyuria and has a high serum osmolality. Positive proof for polyuria resulting from overhydration could have been the use of the water deprivation test. In this test, fluid is withheld until an individual has lost 3% of his body weight. With this amount of fluid loss, the ECF is reduced enough to cause maximal ADH secretion. When the primary problem is overexpansion of the extracellular fluid, the urine output should decrease to 0.5 mg/minute, the urine specific gravity rise to 1.020 or more and the urine osmolality approach 800 mOsm. In the absence of nephrogenic diabetes insipidus, when the above changes in the urine are not observed, it may be assumed that an absolute deficiency of ADH exists. We did not employ this test in our patients because of the obvious danger in subjecting someone to a loss of 3% body weight following major trauma and surgery. Instead we relied upon serum and urine osmolality serum sodium and plasma protein values plus the clinical state of the patient as a guide to the state of hydration. The second most common cause of polyuria in the recently traumatized patient, is acute renal failure, with tubular necrosis, in which the patient goes directly into the diuretic phase without over being oliguric. In this condition there is usuially a rising BUN and serum creatine associated with a urine that contains tubuilar casts and is isotonic with plasma. None of the above mentioned were present in our patients nor was acute tubular necrosis seen on the autopsy specimens.
Other less common causes are nephrogenic diabetes insipidus and diabetes mellitus. The former would manifest itself identically with true ADH deficient diabetes insipidus but would not respond to ADH infusion. The latter can be ruled out by the lack of glucose in the urine and a hypotonic rather than a hypertonic urine. The blood sugar in all our patients were normal. The definitive diagnostic test for DI is the response to exogenous ADH. Intramuscular injection of 10 units of aqueous vasopressin should result in marked diminution in urine volume and a significant increase in the osmolality of the urine. This is precisely what happened in our patients. In Case 1 osmolality studies were not obtained but immediately following injection of ADH the urine flow decreased from 400 ml/hour to less than 100 ml/hour. In the second case, where vasopressin was given the preinjection urine osmolality was 64 mOsm/L and the volume was 310 ml/hour. Following the injection of vasopressing the flow decreased less than 50 ml/hour and the osmolality immediately increased to 212 mOsm/L and eventually to 402 mOsm/L. Similarly in the third patient following the injection of pitressin the urine osmolality increased from 92
Atin. Stirg. * Jantuary 1975
MACHIEDO A?ND OTHERS
to 363 mOsm/L and the urine output declined from an average of 550 ml/hour to 250 ml/hour. A comprehensive review of the literature has revealed only three cases of diabetes insipidus in traumatized patients who had not received closed head injuries. Hanson2 reported two patients and Rottenberg7 another individual, who developed diabetes insipidus from systemic fat emboli, secondary to long bone features. The mechanism responsible for the pituitary dysfunction was thought to be actual disruption of the circulation to the posterior lobe by fat emboli since fat globules were seen in the pituitary vessels in one of Hanson's patients who was autopsied. The syndrome of DI following trauma in which the head is not involved is probably a secondary manifestation of shock. Robinson and Pagliero6 reported the development of DI in a 15-year-old girl following open heart surgery. She was in shock secondary to cardiac tamponade and developed polyuria on the fifth postoperative day. With the use of exogenous pitressin she recovered with no sequalae. Similar recovery has been observed in patients with panhypopituitarism after postpartum hemorrhagic shock. In all probability, the pathogenesis in our patients was due to inadequate tissue perfusion. Fibrin and whole blood thrombi are both commonly seen in the shock state. The former was noted in case 1 in several areas. However, this was not associated with the clinical picture of DIC as with Beernink's patients. Thrombi can also occur as a terminal event. The whole blood thrombi located in the capsule of the pituitary in case 1 and in the parietal vessels in case 3 are
similar to those seen in the cases reported by Sheehan. Since cases 1 and 3 revealed anoxic changes of the cerebral cortex, the mechanism that best explains the syndrome in our patients is shock from hypovolemia with occlusion of vessels resulting in tissue hypoxia and necrosis.
References 1. Beernink, F. F. and McKay, D. G.: Pituitary Insufficiency Associated with Pregnancy, Panhypopituitarism and Diabetes Insipidus. Am. J. Obstet. Gynecol., 84:318, 1962. 2. Hansen, 0. H.: Fat Embolism and Post-traumatic Diabetes. Acta Chir. Scand., 136:161, 1969. 3. Hardaway, R. M.: Clinical Management of Shock. Springfield, III. Charles C Thomas, 1968. 4. Hockaday, T. D. R.: Diabetes Insipidus. Br. Med. J., 2, 210, 1972. 5. Paley, W. B., Inserillo, A. J. and Malkary, J. W.: Puerpersal Diabetes Insipidus and Panhypopituitarism, Obstet. Gynecol., 34:96, 1069. 6. Robinson, R. O., and Pagliero, K. M.: Polyuria After Cardiac Surgery. Br. Med. J., 3:265, 1970. 7. Rottenberg, D. A., Bennett, W. M. and Wolpow, E. R.: Transient Diabetes Insipidus Complicating Systemic Fat Embolization. J. Trauma, 12:731, 1972. 8. Sevitt, S.: Fat Embolism. London, Butterworths & Co., 1962. 9. Sheehan, H. and Whitehead, R.: The Neurohyphysis in Post Partum Hypopituitarism. J. Pathol., 85:145, 1963. 10. Sheehan, H. L. and Murdock, R.: Postpartum Necrosis of the Anterior
Pituitary: Pathological and Clinical Aspects. J. Obstet. Gynaecol. Br. Commonw, 45:456, 1938. 11. Sheehan, H. L. and Stanfield, J. P.: The Pathogenesis of Postpartum Necrosis of the Anterior Lobe of the Pituitary Gland. Acta Endocr. (Kobenhavn), 37:479, 1961. 12. Simmonds, M.: Ueber Hypophysis.