Interpretation of thyroid function tests.

The development of radioimmunoassays over the past 20 years has expanded our knowledge of thyroid physiology and improved our management of thyroid disease. The use of these tools in neonatal screening for congenital hypothyroidism alone has reduced the incidence of mental retardation in the industrialized world. Based on an accurate physical examination, the judicious use of immunoassays for thyroxine, triiodothyronine, and thyrotropin and the use of thyroglobulin and thyroid microsomal antibodies will allow the general physician to confidently delineate common thyroid disorders in the great majority of patients. The additional use of an ultrasensitive thyrotropin assay, thyroid scans, and fine-needle aspiration biopsy will complete the accurate diagnosis of the great majority of thyroid diseases. The ultrasensitive thyrotropin assay may become the universal thyroid function test. The major pitfalls in the use of these tests lies in the variable effect chronic illness has on the most frequently used tests: thyroxine and triiodothyronine. Tests for these thyroid hormones, which in the relatively well outpatient are highly accurate, may in the ill, hospitalized patient become very misleading.

Renal tubular maximum for magnesium in normal, hyperparathyroid, and hypoparathyroid man.

Magnesium infusions were carried out in normal subjects and patients with hypoparathyroidism and primary hyperparathyroidism in order to determine if a tubular maximum for magnesium (TmMg) existed in man and what influence endogenous parathyroid hormone played in renal magnesium handling. The increase in the serum ultrafiltrable magnesium concentration during the magnesium infusions resulted in an increase in urinary magnesium excretion. A TmMg of 1.4 mg/100 ml GF/1.73 m2 was found in the normal subjects under basal conditions. Similarly, TmMg values of 1.4 and 1.3 mg/100 ml GF/1.73 m2, were found in hypoparathyroid and primary hyperparathyroid subjects, respectively. Both were present under basal conditions and neither differed significantly from normal. It is concluded that a TmMg is present in man and that endogenous parathyroid hormone does not appear to play a significant physiological role in renal magnesium homeostasis.

A proposed cellular mechanism for calcium transport in the intestinal epithelial cell.

Intracellular transport of calcium from the apical to the basal-lateral region of the intestinal epithelial cell was investigated in duodenum from normal fed, fasted, and calcium-loaded rats. The process was followed with time using electron microscopy with potassium pyroantimonate to precipitate calcium. The observations made were subjected to morphometric analysis. The specificity of the method was demonstrated in the villus cell by resistance to microincineration and by absence of deposits following exposure to EGTA. Using this method calcium was seen in cells from calcium-fed rats at the microvillus border, in the Golgi zone, and within the internal compartments of the mitochondria. In cells from fasted rats calcium was not seen. Mitochondria were found largely at the apex of the cell and were free of detectable calcium. By 5 min, in the cells of fasted rats given a calcium load, the calcium had reached the Golgi apparatus and the inner mitochondrial compartment. After 15 min mitochondria were heavily loaded with calcium and had moved to the basal region of the cell. These observations suggest that mitochondria play an important role in absorption of calcium and appear to transport this ion from the apex to the basal region of the cell where entry into the capillaries takes place.

Effect of hypophosphatemia on myocardial performance in man.

Severe hypophosphatemia is associated in man with low intracellular stores of ATP and a set of specific cellular dysfunctions. To investigate whether hypophosphatemia affects myocardial performance, we measured cardiac output by thermodilution and calculated stroke work in seven patients with severe hypophosphatemia before, during and after repletion with an intravenous potassium phosphate solution. Mean left ventricular stroke work for these patients increased from 49.57 to 71.71 g-m per beat (P less than 0.01) at the same or higher afterload whereas pulmonary-artery wedge pressure fell from a mean value of 10.1 to 6.7 torr (P less than 0.02). Return of serum phosphate to normal, therefore, improved myocardial stroke work independently of the Starling effect. The mechanism of this improvement in contractile force is unknown but may be related to intracellular availability of ATP.

Hypercalcemia and hypocalcemia.

This report discusses the various aspects of the hypercalcemic and hypocalcemic disorders. We first describe the physicochemical state of serum calcium and the interpretation of a rise or a fall in total serum calcium. The various diseases associated with alterations in the concentration of serum calcium are presented. The clinical manifestations of the hypercalcemic and hypocalcemic disorders and their management are described.

Urinary cyclic AMP analyzed as a function of the serum calcium and parathyroid hormone in the idfferential diagnosis of hypercalcemia.

Urinary cyclic AMP (UcAMP) appropriate for the serum calcium concentration was determined in normal subjects during the base-line state and during alteration in their serum calcium concentrations by saline and calcium infusions. This was compared to the UcAMP in 76 patients with hypercalcemia and 5 patients with hypocalcemia. In 54 of 56 patients with primary hyperparathyroidism, the UcAMP was inappropriately high for their serum calcium concentration, the 2 exceptions having renal failure. In four patients with vitamin D intoxication, sarcoidosis, milkalkali syndrome, and thiazide-induced hypercalcemia and in five patients with hypocalcemia due to hypoparathyroidism, the UcAMP was appropriately low for their serum calcium concentration. In 16 patients with nonparathyroid neoplasms, 10 had UcAMP levels that were inappropriately high suggesting ectopic parathyroid hormone (PTH)-mediated hypercalcemia and 6 had UcAMP levels that were appropriately low suggesting that their hypercalcemia was due to osteolytic factors other than PTH. Correlations between UcAMP, serum calcium concentration, and carboxyl-terminal immunoreactive PTH suggest that random UcAMP is a sensitive accurate reflection of circulating biologically active PTH. If there is adequate renal function (serum creatinine concentration less than 2.0 mg/dl), a random UcAMP expressed as mumol/g creatinine and analyzed as a function of the serum calcium concentration completely separates patients with PTH and non-PTH-mediated hypercalcemia.

Hypoglobulinemia in acromegaly.

We have observed an apparent hypoglobulinemia in 17 of 35 patients (48.6%) with acromegaly. This unexpected finding was persistent and reproducible up to six years for five acromegalic patients, and more than one year for nine other patients. Serum globulin was analyzed by three different methods, and the deficiency was most noticeable in the alpha globulin fraction (alpha1 greater than alpha2). When hypoglobulinemia occurred in control hospital in-patients (11%) it was associated with chronic or severe illnesses, and limited nutritional intake, but similar medical problems were absent in the acromegalic patients. There was no correlation of the hypoglobulinemia in the 35 acromegalic patients to their growth hormone (GH) concentration (r = 0.07), ages, sex, treatment status, or to the seriousness or duration of the acromegaly. The pathophysiology of the apparent hypoglobulinemia in acromegaly is unknown, but may be related to transport and/or disposal of excess growth hormone, or a defect in protein synthesis.

Disodium etidronate therapy for dystrophic cutaneous calcification.

A patient with extensive disabling dystrophic cutaneous calcification and possible scleroderma was treated with orally administered doses of a diphosphonate known as disodium etidronate. This course of therapy seemed to arrest and partially reverse the progression of the calcifying process. Some deep deposits were then seen to dissipate and be partially reabsorbed, while some small superficial depcific deposits were halted in most areas while the patient was under therapy. Clinically, pain was reduced, recurrent abscess formation ceased, and joint mobility was improved.

Inhibition of L-dopa-induced growth hormone stimulation by pyridoxine and chlorpromazine.

One gram of L-dopa was administered orally to 12 male control subjects and induced an increase of growth hormone (GH) secretion. The L-dopa-induced GH response was inhibited by an intravenous infusion of pyridoxine, but pyridoxine did not inhibit the GH response to hypoglycemia. Chlorpromazine also inhibited L-dopa-induced GH stimulation. Glucose concentrations were unaffected by L-dopa, chlorpromazine, and pyridoxine administration in these subjects. The mechanism of the suppressed L-dopa-induced GH response by pyridoxine appears to be mediated by peripheral accleration of the conversion of L-dopa to dopamine, while that of chlorpromazine appears to be mediated through hypothalamic centers. Pyridoxine and chlorpromazine should be added to the list of other factors affecting the response to L-dopa-induced GH stimulation