Iodine and lithium-induced hypothyroidism. Documentation of synergism

Signs and symptoms of hypothyroidism were noted in a patient receiving lithium carbonate for 2 years as prophylaxis against recurrence of mania and depression. When lithium therapy was stopped, the hypothyroidism resolved; but it recurred with the administration of potassium iodide. When potassium iodide therapy was discontinued, the patient became euthyroid. In a second patient chemical evidence of hypothyroidism (fall in circulating thyroid hormone levels, elevation of serum thyrotropin) was noted after he had received 3 weeks of lithium therapy. With the addition of potassium iodide, laboratory evidence of hypothyroidism became more pronounced, and clinical signs of hypothyroidism developed. All abnormalities resolved promptly following the withdrawal of lithium and iodine. These observations suggest that lithium and iodine can act synergistically to produce hypothyroidism and that the combined use of these agents should be avoided.     

Virilizing luteoma of pregnancy. Report of a case with measurements of testosterone and testosterone binding in plasma

Virilizing luteoma of pregnancy with maternal and fetal virilization is reported in a 19 year old woman. Antepartum steroid determinations in the mother revealed an elevated urinary 17-ketosteroid excretion and markedly increased plasma testosterone levels. The percentage binding of testosterone in plasma was lower than expected for normal pregnancy. Surgical removal of the tumor resulted in complete regression of the signs of virilization in the mother and partial regression of the clitoral hypertrophy in the infant. These changes were associated with a return of the biochemical findings to normal.     

Role of circulatory congestion in the cardiorespiratory failure of obesity.

The role of circulatory congestion in the cardiorespiratory dysfunction of massive obesity was investigated in 18 patients. They were hypervolemic and had increased cardiac outputs proportionate to their weight. The average resting left ventricular filling pressure was within the upper limits of normal, but it increased to abnormally high levels with increased venous return of passive leg raising, and further during exercise. The elevations in pressure were associated with high resting central blood volumes which increased significantly with exertion. These findings are consistent with reduced distensibility of the central circulation in these congested patients. Weight reduction was accompanied by a decrease in central blood volumes and restoration of a normal left ventricular response in three of four patients and a return toward normal in one. The improvement in ventricular function with relief of edema and dyspnea. In 14 patients with normal or only minimal alveolar hypoventilation, there were no significant transpulmonary diastolic pressure gradients despite a marked increase in left ventricular end-diastolic pressures. One patient, after regaining weight, subsequently had an abnormal gas exchange and an increased pulmonary vascular resistance. He and two others with severe alveolar hypoventilation demonstrated cor pulmonale on a background of left ventricular dysfunction and congestion of the circulation. Two other patients, the least obese of the group, had hypoventilation and cor pulmonale with normal left ventricular pressures. Hypervolemia and a hyperdynamic state are common features of the obese patients. High cardiac output is maintained despite marked circulatory congestion which may result in generalized anasarca and increased ventricular filling pressures. This clinical syndrome may be present in obese patients without intrinsic heart disease and may be reversible with weight reduction. The central circulatory congestion may contribute to the development of the alveolar hypoventilation syndrome in certain obese patients.     

Methyldopa hepatitis: A report of six cases and review of the literature

Six cases of methyldopa hepatitis, including two in which the patients died are reported; and 77 cases from the literature are reviewed. Patients in whom severe hepatotoxic reactions to methyldopa develop usually complain of prodromal symptoms typical of hepatitis, often with fever, one to four weeks after therapy is initiated. Jaundice, when it occurs, is usually manifest within three months.

Asymptomatic, transient elevations of serum transaminase levels may occur in patients receiving methyldopa. However, since the clinical and histologic features of hepatic injury from methyldopa are indistinguishable from viral hepatitis, it is suggested that the incidence of this iatrogenic disease is higher than generally appreciated.

Serum transaminase levels should be determined at the initiation of therapy with methyldopa and four weeks later. Moreover, any patient who has unexplained fever or the prodromal symptoms of hepatitis should undergo liver chemistry studies immediately.     

Hermansky-Pudlak syndrome. Pulmonary manifestations of a ceroid storage disorder.

The Hermansky-Pudlak syndrome is a form of oculocutaneous albinism, characterized by a qualitative platelet defect and deposition of ceroid-like material throughout the reticuloendothelial system. During a 16 month period five patients with Hermansky-Pudlak syndrome presented with symptoms, chest films and pulmonary function studies consistent with restrictive pulmonary disease. In two patients, lung biopsies revealed diffuse interstitial fibrosis. However, light and electron microscopy demonstrated ceroid-like material within alveolar macrophages. In addition, two patients presented with inflammatory bowel disease with deposition of ceroid-like material in the colon. This disorder appears to be more common than is currently recognized and should be considered in the differential diagnosis of diffuse interstitial pulmonary disease and inflammatory bowel disease. A relationship between the deposition of ceroid-like material and pulmonary fibrosis is discussed in light of recent research concerning inflammatory processes. In view of the serious pulmonary, gastrointestinal and hematologic consequences of this syndrome, there is a need for genetic counseling of these patients.     

The possible importance of aldosterone as well as renin in the long-term antihypertensive action of propranolol

In 50 patients with essential hypertension, propranolol produced a significant decrease in blood pressure. The decrease in mean pressure was greatest in patients classified by a renin sodium nomogram as having high renin hypertension. In turn, blood pressure decreased more in patients with normal renin than in those with low renin levels. Indeed, a net increase in diastolic pressure occurred in the low renin subgroup. These findings confirm the value of pretreatment plasma renin measurements for predicting blood pressure responses to propranolol.Over-all, seven of the 50 patients exhibited increases in mean blood pressure during propranolol treatment. Presumably, this occurred because the minimal suppression of renin-angiotensinmediated vasoconstriction in these patients was insufficient to compensate for the unopposed alpha-sympathetic vasoconstriction unmasked by peripheral vascular beta-blockade. Within this group of patients, there was a significant inverse correlation between control renin values and the amplitude of the pressor response.The decrements in plasma renin were slightly greater in patients classified as responders (decrease in mean blood pressure ≥ 10 per cent) than in nonresponders. However, when the propranolol-induced decrements in aldosterone excretion were taken into account, responders to treatment exhibited far greater decreases than non-responders. Thus, higher levels of aldosterone during treatment may operate to oppose the antihypertensive action of propranolol. Ultimately, this dependency of the blood pressure response upon aldosterone levels is at least partly coordinated with propranolol-induced inhibition of renin release, since we found a significant correlation between changes in these hormones during treatment.     

Membranes nephropathy associated with renal cell carcinoma. Evidence against a role of renal tubular or tumor antibodies in pathogenesis

A patient with the nephrotic syndrome due to membranous nephropathy was found to have renal cell carcinoma. Since membranous nephropathy in patients with malignancies has been attributed to a tumor antigen-antibody complex form of glomerulonephritis, an attempt was made to implicate tumor antigens and/or renal tubular epithelial antigens in the pathogenesis of membranous nephropathy in our patient with renal cell carcinoma. Antibodies directed against tumor antigens and renal tubular antigens and renal tubular eipthelial antigens were sought in his serum and in eluates of his glomeruli; no such antibodies were found. The concurrence of the two renal lesions may have been fortuitous in this patient. However, their association temporally suggests that they were related, and our immunologic studies demonstrate that tumor antigen-antibody complexes are not invariably involved in the pathogenesis of malignancy-associated membranous nephropathy.     

A new observation in the clinical spectrums of erythroleukemia. A report of 46 cases.

Erythroleukemia is a disease manifested by an abnormal proliferation of erythroid and myeloid precursors, generally consisting of a primary erythroid phase (chronic erythemic myelosis), a transition phase involving erythroid and myeloid precursors (erythroleukemia) and, finally, the purely myeloblastic (acute myeloblastic leukemia) phase. The experience at Memorial Sloan-Kettering Cancer Center is reported. Presenting signs and symptoms are consistent with prior reports. The chemotherapy results in the past have been poor; because of the poor results, chemotherapy is started only if one of the following criteria are present: (1) frequent transfusion requirements; (2) rapidly increasing peripheral white blood cell count or percentage of leukemic blast forms; (3) frequent recurrent infectious and/or hemorrhagic complications. A hitherto unrecognized association of erythroleukemia and symptomatic rheumatic disease and numerous immunologic abberations are reported. The symptoms related to this rheumatic disorder do not seem to be relieved by therapy directed at the leukemic process, but rather by the use of simple anti-inflammatory agents.     

Aromatic amines and the pathogenesis of lupus erythematosus

The acetylation pathway of drug metabolism is the pathway by which aromatic amines and hydrazines are metabolized. Hydralazine and procainamide are aromatic amines or hydrazines that are metabolized by this pathway. Persons who are genetically slow acetylators are predisposed to development of lupus from these two drugs, suggesting that the free amine or hydrazine moiety is the inciting agent. When acetylprocainamide was given as an antiarrhythmic drug to patients with procainamide-induced lupus, the disease went into remission, indicating that the free amine group on procainamide had induced the disease. The genetic acetylator phenotypes of persons with idiopathic lupus were studied, and an excess of genetic slow acetylators was observed. This suggests amines or hydrazines induce some cases of this disease. One patient was identified with a lupus-like illness due to occupational exposure to hydrazine itself.     

Symposium on infectious complications of neoplastic disease (Part II). Immunoprophylaxis of varicella-zoster infections

Because it is possible to identify groups of persons with a high risk of varicella development and also because it is possible to anticipate when an attack may occur, immunoprophylaxis for varicella has met with great success. In contrast, the nature of zoster--its unpredictability and low attack rate--makes immunoprophylaxis much more difficult to implement. Varicella may be modified by administration of varicella-zoster immune globulin within three days of a known exposure to the virus. Although interferon has not yet been used in an attempt to prevent or modify varicella in humans, it has been used successfully to abort an outbreak of simian varicella in a monkey colony. Thus it might be clinically useful, particularly for those who cannot be given varicella-zoster immune globulin within three days of exposure. Transfer factor has also been shown to induce at least partial immunity to varicella in children with leukemia. The duration of this protection is unknown, and further study of the efficacy of transfer factor against both varicella and possibly even against zoster seems warranted. Live attenuated varicella vaccine, although still experimental, seems now to be the most practical way to prevent severe varicella in high-risk persons. The vaccine is safe and immunogenic, even in children with underlying leukemia who are still receiving chemotherapy. Studies in Japan, Europe, and the United States have shown that most vaccinated leukemic children who are exposed are protected against severe disease, although mild breakthrough cases have been reported. Varicella vaccine's potential to cause zoster remains under study.