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Elevated levels of free triiodothyronine (fT3) of 8.8 ng/dl (normal range 2.0 to 4.2) and free thyroxin (fT4) of 3.5 pg/ml (0.8 to 1.7) were found in the course of an examination of a 53-year old patient due to a planned hysterectomy. As thyrotropin (TSH) also was elevated with 5.8 mU/l (0.4 to 4.5), these findings corresponded to an inappropriate secretion of TSH (IST). Additional examinations revealed a blunted rise of TSH secretion after i.v. injection of 200 micrograms thyrotropin releasing hormone (TRH) as well as lacking suppression of TSH secretion after oral doses of 75 micrograms T3 during one week. alpha-TSH levels with 3.7 micrograms/l were elevated in comparison to a matched normal sample just as the molar ratio alpha-TSH/TSH with 6.95 and sex hormone-binding globulin (SHBG) with 175 nmol/l and showed an absence of inhibition in the T3 suppression test. These results were suggestive of neoplastic inappropriate secretion of TSH (nIST) due to a TSH-secreting pituitary adenoma. In concordance, the magnetic resonance imaging (MRI) showed a 1 cm tumor in the sella. The adenoma could also be visualized by 111In-octreotide and 123I-epidepride scintigraphies of the pituitary gland. After transsphenoidal resection, histological examination of the tumor resulted in the finding of a TSH-secreting adenoma. Postoperative TSH levels were not detectable, indicating the complete removal of the adenoma. Levels of fT3 and fT4 were slightly below normal with 1.9 pg/ml and 0.7 ng/dl, respectively. A control scintigraphy with 111In-octreotide following an equivocal MRI showed no uptake in the pituitary.

Iodine deficiency, intrathyroidal defects of thyroxine synthesis and morphological defects of the thyroid gland are the causes for connatal hypothyroidism of various degrees. Morphological defects include the most severe forms of cretinism due to aplasia of the gland as well as various more milder forms following application of iodine or antithyroidal drugs to the mother or TSH deficiency of the newborn. Due to general TSH-screening programs, more will be learned about the still not fully understandable etiology of connatal hypothyroidism.

The identification of pituitary ACTH and TSH producing cells was performed by histological staining at the isoelectric points (pH levels: 4.6 and 5.2 respectively) of these hormones in cat. Intensity of stained material in the hormone producing cells was determined by microphotometric technique. By the application of hormones influencing the pituitary ACTH and TSH producing relevant changes in pituitary cells could be detected.

A simple test with 40 mg of oral TRH after overnight fasting was developed and can be characterized as follows: This short oral TRH test has been found to be a most valuable thyroid function test for detection of hyper- and hypothyroidism. It is as reliable as the intravenous TRH test. Oral TRH produces much stronger and more prolonged TSH stimulation similar to that of a depot preparation. Therefore, the incidence of euthyroid controls with absent or subnormal TSH response to TRH is definitely lower than after intravenous TRH. In patients with low TSH response after i.v. TRH the oral TRH test is of particular diagnostic value in distinguishing euthyroid function from TSH suppression or pituitary failure. 40 mg or oral TRH produces reliable stimulation of T3 in most euthyroid subjects. In patients with hyper- and hypothyroidism no increase of T3 is obserable. Oral TRH allows simultaneous assessment of pituitary TSH and thyroid reserve in a single test. The practical advantages (side effects in only 2% [for i.v. TRH 60%], only 1 or 2 blood samples, fewer sampling errors and no i.v. injection) outweigh the disadvantages (longer duration of the test, dependence on food intake and gastrointestinal absorption).

Analyzing the clinical data of 258 patients whose treatment after thyroid surgery was followed by the TRH-stimulation test over a period of 5 years we found that in 130 patients (93%) sufficient substitution was achieved. The increase in the TSH-level after TRH-stimulation was less than 10 muE/ml. There was no case of recurrence in this group. In 18 patients (7%) who admitted taking medication irregularly, there was an average increase in TSH-level of 16,7 muE/ml. There were two cases of recurrence in this group. The recurrence rate after thyroid surgery can be decreased by sufficient medical treatment resulting in an increase of TSH-level less than 10 muE/ml after TRH-stimulation, providing there is a close follow-up and a high incidence of patients' cooperation.