Thyrotropin Reserve Research Articles

Isolated Thyrotropin Deficiency Secondary to Primary Empty Sella in a Patient with Differentiated Thyroid Carcinoma: An Indication for Recombinant Thyrotropin

The primary empty sella syndrome is a common radiographic finding that is rarely associated with clinical pituitary dysfunction. Studies using dynamic endocrine testing, however, have shown altered pituitary reserve in some patients with the primary empty sella syndrome. We describe a patient with a primary empty sella and an isolated deficiency of thyrotropin reserve. This case is complicated by the presence of an aggressive metastatic papillary epithelial carcinoma of the thyroid. Standard treatment with radioactive iodine was unlikely to be effective in this patient due to the need for adequate thyrotropin (TSH) stimulation of the malignant tissue to optimize uptake of radioactive iodine by the tumor cells. Consequently, this patient was treated with human recombinant TSH before receiving radioactive iodine. The utility of this novel therapeutic agent and a review of hormonal abnormalities associated with the primary empty sella are also discussed.

Recovery of Pituitary Thyrotropic Function after Withdrawal of Prolonged Thyroid-Suppression Therapy

The pattern of thyrotropin secretion was analyzed in seven euthyroid women, before and after withdrawal of long-term thyroid hormone, by serial measurements of thyroid 131l uptake, serum thyroxine, tri-iodothyronine, and thyrotropin concentrations, and the response to thyrotropin-releasing hormone. During exogenous hormone administration, 131l uptake was suppressed, and serum thyrotropin concentrations before and after administration of thyrotropin-releasing hormone were undetectable. After withdrawal of exogenous hormone, thyrotropin secretory function was transiently impaired, as indicated by undetectable basal thyrotropin concentrations together with absence of response to thyrotropin-releasing hormone, and subsequently by normal values of basal thyrotropin concentration and normal responses to releasing hormone while serum thyroxine and tri-iodothyronine concentrations were subnormal. Decreased thyrotropin reserve persisted for two to five weeks. Detectable values of serum thyrotropin (less than 1.2 muU per milliliter) and a normal 131l uptake usually occurred concurrently in two to three weeks. Serum thyroxine concentration returned to normal at least four weeks after hormone withdrawal.

Thyrotropin-Releasing Hormone as a Pituitary-Function Indicator

Pituitary thyrotropin reserves were tested with intravenous injections of 500μg of lopremone (synthetic thyrotropin-releasing hormone) in eight normal subjects, ten patients with complete hypopituitarism, and ten with incomplete hypopituitarism. Normal subjects had a mean basal thyrotropin-stimulating hormone level of 2.3μ± 1.8μU/ml and attained a mean maximal thyrotropin-stimulating hormone level of 19.8μ ± 8.2μU/ml 20 to 30 minutes after injection; no marked response occurred in patients with complete hypopituitarism. Of the incomplete hypopituitarism group, two had subnormal responses and were clinically hypothyroid. The others, clinically euthyroid, had normal responses compared to normal subjects of similar ages. Growth hormone reserve in this group was first to show impairment, whereas adrenocorticotropic hormone and thyrotropin-stimulating hormone reserves were last affected. The lopremone stimulation test is useful and specific in evaluating pituitary thyrotropin reserve.

Assessment of thyrotropin-releasing hormone and thyrotropin reserve in man.

Endogenous thyrotropin-releasing hormone (TRH) reserve and pituitary thyrotropin (TSH) reserve were assessed in four normal subjects, three patients post-cryohypophysectomy, one patient with a hypothalamic lesion secondary to trauma, and four patients with Sheehan's syndrome. TSH reserve was determined by the immunoassayable TSH response to 500 mug TRH given i.v. (TRH stimulation test). TRH reserve was assessed by the rebound response in thyroidal iodine release (TIR) following withdrawal of pharmacologic doses of prednisolone (glucocorticoid withdrawal test). When compared with normals, the post-cryohypophysectomy patients demonstrated parallel impairment of TRH stimulation and glucocorticoid withdrawal testing. The patient with the hypothalamic lesion and the four patients with Sheehan's syndrome all had normal TRH stimulation tests, indicating adequate TSH reserve capacity, yet had abnormal glucocorticoid withdrawal tests, indicative of impairment in endogenous TRH reserve or neurohumoral transport. Three of the patients (hypothalamic injury and two Sheehan's) with impaired TRH reserve were euthyroid. THE FOLLOWING CONCLUSIONS WERE REACHED: (a) A combination of the TRH stimulation test and glucocorticoid withdrawal test may allow for differentiation between pituitary and suprahypophyseal disorders. (b) Certain cases of Sheehan's syndrome appear to have impaired endogenous TRH reserve or transport. (c) Euthyroidism can be maintained in spite of diminished TRH reserve.

Synthetic Thyrotropin Releasing Factor as a Test of Pituitary Thyrotropin Reserve

The iv administration of 0.5 mg of synthetic thyroptropin releasing factor (TRF) to control subjects increased plasma TSH from baseline levels of 2.1 ± 0.01 μU/ml to peak values of from 8.5–27 μU/ml. Plasma TSH levels in subjects with primary myxedema were elevated and rose further following TRF. In seven of 16 euthyroid subjects with pituitary tumors, peak values of plasma TSH following TRF ranged from 2.5–6.5 μU/ml indicating limited reserve for TSH secretion. Subjects with hypothyroidism secondary to Sheehan’s syndrome or pituitary tumors did not alter their plasma TSH levels following TRF indicating inadequate pituitary function. Plasma TSH rose normally following TRF in five subjects with TSH deficiency in the absence of a known organic pituitary lesion. This latter group of subjects may have TRF deficiency as a cause of their decreased TSH secretion.

Effect of Cold Exposure on Serum Thyrotropin

To study the effect of cold exposure on serum thyrotropin, normal male volunteer subjects were exposed to 2–4 C and blood samples were obtained every 10 min for 1 hr. Serum TSH measured by radioimmunoassay did not change in 14 subjects. Administration of large doses of dexamethasone, testosterone propionate and conjugated equine estrogen separately or combined did not alter the TSH level in response to this cold exposure. Severe hypothermia in 11 patients undergoing open heart surgery failed to elevate serum TSH. In rats exposed to 3–4 C for 30 and 240 min. there was a significant increase in serum TSH measured by both bioassay and radioimmunoassay. The results indicate that acute cold exposure in man will not serve as a test of the integrity of the hypothalamic-pituitary TSH axis or as a means of testing pituitary thyrotropin reserve.