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Pituitary disorders can be diagnosed more readily and precisely as a result of two recent advances: development of radioimmunoassays for direct measurement of each pituitary hormone in blood, and availability of hypothalamic hormones for use in provocative tests for secretion of thyroid-stimulating hormone, prolactin, and gonadotropic hormones.
The hypophyseal gonadotrophin LH reserve was studied in 9 adult women, 5 of whom were suffering from nervous anorexia (N.A.) and 4 normal, by means of subcutaneous injection of 50 mcg of synthetic GN-RH. Basal values of plasmatic LH proved to be significantly lower in N.A. than in the controls where the response to GN-RH was prompt. In patients with N.A., on the other hand, response was practically absent and differences were significant at all stages of the test. The parallel study of basal steroiduria and following methopirone confirmed the torpid hypophyseal response in N.A. These findings confirm previous personal reports and indicate that the GN-RH test is a useful technique for diagnostic and prognostic definition of N.A.
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Fifteen patients, age 16 to 55, presented with amenorrhea-galactorrhea-hyperprolactinemia. Pituitary function was evaluated by bolus injections of insulin, luteinizing hormone-releasing hormone (LHRH), and thyrotropin-releasing hormone (TRH) in 13 and by LHRH and TRH in 2. Responses to growth hormone (GH), thyroid-stimulating hormone (TSH), cortisol (F), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin were measured. GH, TSH, and F responses were normal in most cases. LH responses were decreased (P less than 0.025) in patients with abnormal sellar tomography, whereas FSH responses tended to decrease with elevated prolactin levels. Prolactin responses were absent in five of the seven cases which could be evaluated. The clinical value of such testing appears to be limited to an individualized basis, although some prognosis of ovulatory response to bromocriptine therapy may be obtained from the gonadotropin response.
The elevated level of growth hormone after moderate standardized physical exercise was compared with that induced by intravenous arginine infusion and by insulin induced hypoglycemia in children with normal pituitary function. Tests were performed on 49 prepubertal children (34 boys and 15 girls); in 42 cases the increase was significant for all three tests, in 5 cases the response was minimal after insulin stimulation but normal after arginine and physical exertion; in 1 case arginine produced no response but the other tests were positive; in 1 case there was a response to arginine but none to insulin or physical exertion. The results indicate that frequently more than one test is necessary for the diagnosis of normal pituitary function; physical exertion being a physiologic test, is simple to perform, acceptable to the children and without side effects. It appears the test of first choice because it can be used in patients seen ambulatorily, other tests being performed in case of doubt or negative response.
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A total number of 23 patients treated with human growth hormone were retested by use of a combined pituitary stimulation test. Plasma concentrations of GH, FSH, LH, TSH, T4, T3, prolactin (PRL), ACTH and cortisol were measured before and after stimulation with hypoglycemia, TRH and LHRH. The test was performed in patients with persistent GH deficiency (group A) and patients with transitory GH deficiency (group B). In group A a normal pubertal development was found in three patients, whereas in prepubertal subjects the FSH/LH responses were smaller than those of prepubertal patients in group B. Also plasma ACTH increase was less pronounced in group A patients than in group B. In contrast, the plasma TSH and PRL responses were more sustained in group A than in group B. The secretory pattern of TSH and PRL was comparable in the two groups of patients. Thus, in patients with persistent GH deficiency additional multiple disturbances of the hypothalamic-pituitary function often appeared whereas in most patients with transitory GH deficiency the combined pituitary test was normal at the reinvestigation.
A combined test of anterior pituitary function was used on 21 normal children. It shows that a comprehensive evaluation can be made of growth hormone, thyroid stimulating hormone, adrenocorticotrophic hormone, and gonadotrophin reserve. Simultaneous assessment of those peripheral glands associated with the anterior pituitary is possible by the measurement of thyroid hormones, cortisol, and gonadal steroids. The procedure can be completed in 4 hours with minimum inconvenience and distress to the child.
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The following examinations, including the estimation of urinary neutral steroid metabolites, plasma cortisol, the percentage of unbound-cortisol, cortisol production rate, plasma adrenocorticotrophin (ACTH), dexamethasone suppression test, ACTH stimulation test, metopirone test, lysine-vasopressin (LVP) test and insulin tolerance test, were conducted in 16 patients with Cushing's syndrome for the presence of hypercoticism and for identifying the cause of this syndrome. Of these tests, the measurements of plasma cortisol late in the day and single dose dexamethasone suppression test were most useful for the diagnosis of hypercorticism because of their reliability and simplicity. Urinary 17-KGS, THF/THE ratio, cortisol production rate and low dose dexamethasone suppression test were also useful, whereas insulin test and LVP test were less valuable for this purpose. For the identification of the causes of this syndrome, lysine vasopressin test and metopirone test were most reliable, and plasma ACTH was also useful for this purpose, whereas insulin test and ACTH stimulation test were less valuable.
Intravenous insulin tolerance tests and thyrotropin-releasing hormone (T.R.H.) stimulation tests were performed in nine massively obese women and six lean female controls and the prolactin, growth hormone, and cortisol responses were measured. A combined pituitary function test (insulin, T.R.H., and gonadotropin-releasing hormone) was performed in eleven other massively obese women. In the obese women to whom insulin was given separately there was no prolactin release, and growth hormone and cortisol responses were impaired. T.R.H. stimulation produced a prolactin response which was subnormal. These changes were not apparent in the obese women in whom a combined pituitary function test was performed. The results suggest an alteration of hypothalamic function in massive obesity.
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To investigate hypothalamic-pituitary functions and the primary site of the lesion in idiopathic pituitary dwarfism, various pituitary function tests, especially the pituitary hormone responses to the hypophysiotropic hormones were studied in 23 patients with idiopathic pituitary dwarfism. A few cases showed slight responses of GH to GH stimulation tests. Gonadotropin deficiencies were most frequently noted among pituitary hormones. The basal levels and the responses of plasma LH and FSH to LH-RH test were diminished markedly in all of the cases except in 5 cases with isolated GH deficiency. Responses of LH and FSH to LH-RH improved markedly after a long term administration of LH-RH for a period of one month in 2 patients with gonadotropin deficiency. As to TSH axis, half of the cases accompanied hypothyroidism. However, the responses of TSH to TRH were normal in all of the cases regardless of the thyroid function. The basal levels and the responses of plasma cortisol and 11-deoxycortisol to the rapid metopirone test were also impaired in about half of the cases. Basal levels of plasma prolactin were normal in all of the cases and the responses of prolactin to TRH were normal in cases with normal thyroid function, but slightly delayed in cases with hypothyroidism. It is concluded from the above observations that the incidences of various pituitary hormone deficiencies were quite high in this disorder and hypophysiotropic hormone deficiencies may cause pituitary hormone deficiencies. Therefore, it is suggested that the primary site of the lesion in this disorder might be at the hypothalamus.
Anterior pituitary function tests (ITT, TRH test and LH-RH test) were performed on 10 patients with intracranial lesions other than hypothalamo-pituitary tumors. These lesions were 8 brain tumors and 2 aneurysms. Relatively high doses of glucocorticoid were administered in pre- and post-operative period to all the cases. Preoperative study showed a slightly low response of GH and FSH in one case and a low TSH response in 2 cases. ACTH, LH and PRL were normal in all the cases. Postoperative study was performed about 10 days after ceasing of glucocorticoid. Postoperative data revealed that anterior pituitary function tests did not show any significant changes after surgeries in all the patients.
Hypothalamic hypopituitarism has been associated with the intermittent intracranial hypertension of "normal-pressure" hydrocephalus. Six patients with this condition were studied endocrinologically; five showed evidence of hypothalamohypophyseal insufficiency, and, though only one needed treatment, all needed continued assessment of their endocrine state during follow-up. Thus, hypothalamohypophyseal dysfunction is more common than might be expected. Tests of anterior pituitary function should be preformed before surgical intervention, as such dysfunction may adversely affect survival and the response to ventricular shunting.