Effect of Hypocalcemia on Hormonal Responses to Thyrotropin-Releasing Hormone HAROLD E. CARLSON AND ARNOLD S. BRICKMAN Medical and Research Services, Veterans Administration Wadstvorth Hospital Center and Department of Medicine, UCLA School of Medicine, Los Angeles, California ABSTRACT. The effects of chronic hypocalcemia on pituitary and thyroidal responses to TRH were studied in six euthyroid and three mildly hypothyroid subjects with surgical hypoparathyroidism or pseudohypoparathyroidism. In the euthyroid patients, increments in serum TSH, T3, and T4 were equal under hypocalcemic or nonnocalcemic conditions; however, a slightly but significantly lower basal serum T3 during hypocalcemia in conjunction with unaltered basal serum T4 and reverse T3 levels suggests that hypocalcemia may alter peripheral metabolism of T4 and/or T3. Hypothyroid subjects showed more variable responses to hypocalcemia; after restoration of normocalcemia, two patients demonstrated greater

T

HE PRESENCE of calcium has been shown to be necessary for many endocrine secretory processes. A requirement for calcium has been demonstrated for pituitary and pancreatic islet secretion in vitro (1-3), while animal studies have indicated a suppressive effect of hypocalcemia on insulin secretion in vivo (4,5). In hypocalcemic states in man, insulin secretion has recently been shown to be modestly blunted (6,7). This investigation reports studies of pituitary and thyroid function in human hypocalcemic disorders, as assessed by hormonal responses to thyrotropin-releasing hormone (TRH). Materials and Methods Patients

serum T3 increments following TRH and lower TSH levels, suggesting an impairment of thyroidal secretion by hypocalcemia, while the third showed no effect of hypocalcemia on TSH, T;i, or T4 responses to TRH. Hypocalcemia had no effect on prolactin responses to TRH in the combined group of euthyroid and hypothyroid patients. Since only minor effects on basal or TRH stimulated hormone levels were seen in all patients, it is concluded that hypocalcemia rarely has clinically significant effects on pituitary secretion of TSH and prolactin and thyroidal release of T4 and T3. (J Clin Endocrinol Metab 45: 209, 1977)

were euthyroid by clinical and laboratory parameters; two of these six had pseudohypoparathyroidism, while four had surgical hypoparathyroidism. Three subjects with mild primary hypothyroidism (basal serum thyrotropin >5 /u,U/ml) were also studied; two had pseudohypoparathyroidism and one had surgical hypoparathyroidism. Endocrine testing Testing with thyrotropin-releasing hormone (TRH), kindly supplied by Abbott Pharmaceuticals, was performed while subjects were hypocalcemic and again when serum calcium had been normalized for 10-180 days by treatment with supplemental vitamin D and calcium. Following an overnight fast, 500 /ug of TRH was given as an iv bolus through an indwelling butterfly needle; serum samples were obtained for hormonal assay before and over a 4-hr period after TRH administration.

Nine patients with hypocalcemia, ages 11-61, participated in the study; all gave informed consent to the procedures performed. Six subjects

Hormone assays

Received August 25, 1976. Supported by The Medical Research Service of the Veterans Administration. Reprint requests to: Harold E. Carlson, M.D., Endocrinology Section, Wadsworth VA Hospital, Wilshire & Sawtelle Blvds., Los Angeles, California 90073.

Serum thyrotropin (TSH) was measured in the radioimmunoassay of Pekary et al. (8); normal subjects studied in our laboratory have serum TSH levels less than 5/xU/ml, with a mean value of 1.5 ± 1.0 (SD) /uU/ml. Serum prolactin (PRL) was measured according to the radio-

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immunoassay method of Sinha et al. (9), using material supplied by the National Pituitary Agency, NIAMDD; the mean serum PRL in a group of 40 normal male subjects was 5.7 ± 3.0 (SD) ng/ml and 7.7 ± 4.3 ng/ml in 30 females. Serum 3,5,3'-triiodothyronine (T3) and thyroxine (T4) were measured in specific radioimmunoassays, previously described (10); normal serum T3 was 148 ± 32 (SD) ng/dl and normal serum T4 was 7.9 ± 1.5 /ng/dl. Serum 3,3',5'-triiodothyronine (reverse T3, rT3) was kindly measured by Dr. I. J. Chopra using a previously published radioimmunoassay method (11); mean serum rT3 levels in normal subjects were 41 ± 10 (SD) ng/dl. For each hormone, all samples from a single subject were run in the same assay. Total serum calcium was measured by atomic absorption spectrophotometry; the normal range

for serum calcium in our laboratory is 8.8-10.5 mg/dl. Serum glucose was assessed by a glucose oxidase method. Student's paired t test was used for statistical comparisons. Results

Euthyroid

subjects

In the euthyroid subjects, mean serum calcium when hypocalcemic was 6.76 ± 0.30 (SEM) mg/dl and 9.93 ± 0.35 mg/dl when normocalcemic. Basal serum TSH and the TSH response to TRH were unaltered

JCE & M . 1977 Vol 45 • No 2

by the presence of hypocalcemia (Fig. 1); basal and TRH-stimulated levels of T4 were similarly unchanged (Fig. 2A). Mean basal serum T 3 (average of —15 min and zero time values) was significantly (P < 0.05) lower during hypocalcemia (149 ± 15 ng/dl) than during normocalcemia (166 ± 13 ng/dl), as were serum T3 values at the zero and +240 min time points (Fig. 2B). The increment of T 3 over baseline following TRH was identical in hypocalcemia and normocalcemic phases, however. Similarly, the mean ratio of basal T3/T4 was significantly (P < 0.05) lower during hypocalcemia (18.0 ± 1.3 (SEM)) than during normocalcemia (21.0 ± 1.0). Basal serum levels of reverse T3, the alternative metabolite of monodeiodination of T4, were unchanged by hypocalcemia; mean basal serum rT3 during hypocalcemia was 26.7 ±1.8 (SEM) ng/dl, not significantly different from the value of 27.7 ± 1.0 ng/dl obtained durii z the normocalcemic period. The ratio 0 basal 1T3/T4 was similarly unchanged. Although the time of the TSH and 1 , peaks after TRH was not altered by hypoc

Effect of hypocalcemia on hormonal responses to thyrotropin-releasing hormone.

Effect of Hypocalcemia on Hormonal Responses to Thyrotropin-Releasing Hormone HAROLD E. CARLSON AND ARNOLD S. BRICKMAN Medical and Research Services,...
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