Water handling in patients receiving haloperidol decanoate.

OBJECTIVE: To determine whether water handling in patients receiving haloperidol decanoate (HD) was impaired. DESIGN: Prospective, controlled trial of water handling in patients without symptomatic hyponatremia receiving HD. Eligibility for study inclusion required that patients had received HD for at least 4 months, were not taking any medication reported to cause inappropriate antidiuretic hormone secretion or hyponatremia (excluding haloperidol), and would agree to participate in the study. An age- and gender-matched healthy control subject was enrolled for each study patient. Baseline laboratory values were obtained within 48 hours prior to the standard water-loading test to screen for abnormalities in electrolytes, kidney function, and liver function. A 20-mL/kg water-load test was administered to each patient. Urine volume and osmolality were measured every hour for 4 hours. SETTING: A community mental health (CMH) outpatient psychiatric facility for the patients receiving HD and Saint Mary's Health Services for the controls. PARTICIPANTS: Fifteen patients receiving HD from the CMH facility and 15 age- and gender-matched control subjects were enrolled. MAIN OUTCOMES MEASURES: Impaired water handling was defined as a failure to dilute urine to less than 100 mmol/kg or a failure to excrete more than 65% of a water load in 4 hours. RESULTS: Five patients receiving HD were excluded because of protocol refusal or violation. Five of 10 evaluable patients receiving HD had abnormal water handling. Two of these could not lower their urine osmolality to less than 100 mmol/kg, 2 could not excrete more than 65% of the water load, and 1 did not meet either criteria. None of the healthy volunteers had abnormal free water handling. The difference between the study patients and the control subjects was statistically significant (p = 0.0097). CONCLUSIONS: Fifty percent of our study patients receiving HD had abnormal free water handling. This finding, combined with our clinical observations of symptomatic hyponatremia in other patients receiving the drug, suggests the need to investigate the incidence of hyponatremia and to design a useful screening tool to identify patients at risk. In the meantime, clinicians should be aware of the potential for impaired water handling in patients receiving HD.

Hypothalamic-pituitary function following bromocriptine therapy in patients with prolactinomas.

Bromocriptine in a dose of 5 mg daily was given to 18 patients with prolactinomas to promote resumption of menses, to overcome infertility and as a primary treatment for the tumor. Serum prolactin levels fell to within the normal range in 95% of the patients by 12 weeks of therapy. The prolactin response to TRH stimulation was significantly less than before treatment; however, the percent maximum increment was significantly higher. There was no significant change in pituitary reserve of the other hormones. Seven pregnancies occurred during treatment. All the pregnancies have been progressing normally. All patients have already been delivered of healthy babies, including one set of twins. It is suggested that follow-up studies of the various pituitary hormones be conducted on patients on maintenance bromocriptine treatment. In addition, bromocriptine treatment might be used to promote fertility in patients with prolactin-secreting microadenomas.

Secondary hyperparathyroidism caused by oral contraceptives.

Secondary hyperparathyroidism developed on two separate occasions in a patient taking an oral contraceptive (OC) in a mixture of norethindrone and mestranol (Ortho-Novum 1/80). The probable cause of this condition is an estrogenic inhibition of the calcium mobilizing effect of parathyroid hormone (PTH) or vitamin D. The possible consequences of OC therapy in this patient and patients like her include those of milk hypocalcemia, moderate hypophosphatemia, or the neurotoxic actions of excessive levels of circulating PTH. One should also consider the possible role of OC therapy in patients with unexplained parathyroid hyperplasia and with tertiary hyperparathyroidism.

Simplifying the diagnosis of diabetes insipidus in children.

We simplified the procedures for identifying children with diabetes insipidus by using the relationship between urine and plasma osmolality (Uosm and Posm). We defined the normal Uosm-Posm relationship as the area within the 95% confidence regions for pairs of osmolality measurements obtained from normal children during periods of free access to fluids and after oral hydration. In 13 patients with diabetes insipidus, Uosm-Posm coordinates were outside these regions in 50 of 64 pairs (one to ten per patient) during periods of free access to fluids. After three hours of fluid deprivation, the Uosm-Posm relationship was abnormal in 12 patients; the 13th was unable to void. For those with a normal Posm, and Uosm less than Posm, another pair of osmolality measurements after three hours of fluid restriction should determine the diagnosis.

Antidiuretic responses to injected desmopressin, alone and with indomethacin.

Desmopressin (dDAVP) is a synthetic analog of arginine vasopressin which generally has been very effective, used intranasally, in the treatment of diabetes insipidus. There are several clinical situations, however, where a parenteral route of administration would be preferable. Using 6 patients with diabetes insipidus, we have shown a dose-response relationship between 0.5 and 4 microgram of dDAVP injected sc. The nonsteroidal, antiinflammatory agent, indomethacin, augments the magnitude, but not the duration, of the response to 0.5 microgram dDAVP. These observations suggest that injected dDAVP, generally in the amount of 1 or 2 microgram, would be a valuable agent in the treatment of diabetes insipidus and that combined therapy with indomethacin is probably not warranted.

Permanent diabetes insipidus following head trauma: observations on ten patients and an approach to diagnosis.

Permanent diabetes insipidus following head trauma is uncommon, but potentially fatal. The neurologic, roentgenographic, and endocrinologic findings in ten patients with this condition are reported. Eight of the patients were males under the age of 35 years. Unconsciousness (nine) and skull fracture (seven) were frequent findings. Cranial nerve damage (four) and anterior pituitary hormone deficiency requiring replacement (one) were less frequent. An automobile accident caused the trauma in six patients. Standard water deprivation tests revealed that five of the patients had total deficiency of antidiuretic hormone (ADH), and the other five had partial deficiency. The diagnosis of diabetes insipidus was markedly simplified by using a new screening test based on comparing urine and plasma osmolality in candidates with those of normal subjects.

Studies on the attainment of normocalcemia in patients with pseudohypoparathyroidism.

Basal serum calcium and parathyroid hormone (PTH) levels were measured, and urinary excretion of cyclic adenosine monophosphate (AMP) and phosphate was determined before and after the infusion of 250 U of PTH in four patients with pseudohypoparathyroidism when they were hypocalcemic and again when they spontaneously became normocalcemic. These data were compared to those observed in a group of patients with pseudohypoparathyroidism before and after they became normocalcemic after treatment with vitamin D and calcium. Serum PTH levels were very high in patients with untreated pseudohypoparathyroidism and decreased, although not to normal, when normocalcemia occurred either spontaneously or through treatment. Of the four patients who became normocalcemic spontaneously, basal and PTH-stimulated urinary excretion of cyclic AMP, and clearance of phosphate increased. These changes were all significantly different from the changes which occurred when patients became normocalcemic as a result of treatment with vitamin D anc calcium. The factors which govern the apparent increased renal sensitivity to endogenous and exogenous PTH when normocalcemia develops spontaneously in patients with pseudohypoparathyroidism remain to be explained. However, these changes are dissimilar from those which occur from treatment with vitamin D anc calcium.

Albright's osteodystrophy in a patient with renal hypercalciuria.

We have investigated an 18-yr-old hypercalciuric female with features of both renal hypercalciuria and pseudohypoparathyroidism. She had increased circulating parathyroid hormone levels, which are common to both diseases. She also had a modest hypocalcemia and low normal basal cAMP excretion, both of which are more likely to occur in pseudohypoparathyroidism. She also had Albright's osteodystrophy, which is frequent in patients with pseudohypoparathyroidism and has never been reported in patients with renal hypercalciuria. In contrast to patients with pseudohypoparathyroidism, her serum 1,25-dihydroxycholecalciferol level was increased and her renal responses to parathyroid hormone infusion, including renal calcium reabsorption, were normal. This patient, therefore, raises the possibility that some patients with renal hyperalciuria may have a forme fruste of pseudohypoparathyroidism.

Fulminating hypercalcemia and markedly increased nephrogenous cyclic AMP in a patient with transitional cell carcinoma of the bladder.

Refractory hypercalcemia developed suddenly in a patient who had undergone a radical cystectomy for an anaplastic transitional cell carcinoma of the bladder. A normal serum parathyroid hormone (PTH) value was obtained by immunoassay while the patient had hypercalcemia and unimpaired renal function. This normal PTH value in the presence of hypercalcemia was consistent with his hypercalcemia being secondary to excessive amounts of circulating PTH. The finding of increased nephrogenous cyclic AMP, however, provided the definitive diagnosis of hyyperparathyroidism. Since autopsy revealed that there was no residual tumor in the bladder area, only evidence of metastatic disease, and since the parathyroid glands were not hyperplastic or adenomatous, we attributed this patient's hypercalcemia to hyperparathyroidism due to the ectopic production of PTH by a metastasis from the transitional cell carcinoma of the bladder.

Profiles of antinuclear antibodies in systemic rheumatic diseases.

The prevalence of different antinuclear antibodies was examined in systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, progressive systemic sclerosis, dermatomyositis, discoid lupus erythematosus, and mixed connective tissue disease. Antibody to Sm antigen (a nuclear acidic protein) was found almost exclusively in serums of patients with systemic lupus erythematosus, suggesting that this antibody might be a "marker" antibody for this disease. However, antibodies to native DNA and to nuclear ribonucleoprotein were found in a variety of systemic rheumatic diseases. In systemic lupus erythematosus, antibody to native DNA was present in high titer but in other rheumatic diseases in low titer. Antibody to nuclear ribonucleoprotein occurred in certain other systemic rheumatic diseases besides the mixed connective tissue disease syndrome. These studies showed that there were distinct profiles of antinuclear antibodies in certain systemic rheumatic diseases, characterized by the presence or absence of certain antibodies and by differences in their mean titers.