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Rationale: The utility of fractional exhaled nitric oxide (FENO) suppression (FeNOSuppT) to identify non-adherence to inhaled corticosteroid (ICS) treatment has previously been reported, but whether it can predict clinical outcome remains unclear. Objectives: We examined the utility of FeNOSuppT in prediction of progression to biologic agents or discharge from specialist care. Methods: FeNOSuppT was measured at home using remote monitoring technology of inhaler use alongside daily FENO measurement over 7 days. Long-term clinical outcomes in terms of progression to biologic agent or discharge from specialist care were compared for non-suppressors and suppressors. Measurements and main results: Of the 162 subjects, 135 successfully completed the test with 81 (60%) positive FENO suppression tests. Subjects with a negative FeNOSuppT were more likely to proceed to biologic therapy (39 of 54 patients, 72%) compared to those with a positive FeNOSuppT (35 of 81 patients, 43%, p=0.001). In subjects with a positive FeNOSuppT, predictors of progression to biologic therapy included higher dose of maintenance steroid at initial assessment and prior intensive care unit admission. These subjects had a significant rise in FENO between post-suppression test and follow-up (median, 33 (IQR 25–55) versus 71 (IQR 24–114); p=0.009), which was not explained by altered corticosteroid dose. Conclusions: A negative FeNOSuppT correlates with progression to biologic therapy. A positive FeNOSuppT, with subsequent maintenance of “optimised” FENO, predicts a subgroup of patients in whom asthma control is preserved with adherence to high-dose ICS/long-acting β2 agonist and who can be discharged from specialist care., A positive FENO suppression test can identify non-adherence. Maintenance of “optimised” FENO by sustained adherence to inhaled therapy predicts patients who are likely to maintain control with high-dose inhaled therapy without the need for biologics. https://bit.ly/3cRpQ5B

A case of a 50-year-old woman who was referred for the evaluation of possible ACTH-dependent Cushing’s syndrome (CS) is described. The localisation of ACTH-dependent CS remains difficult despite many advances in diagnostic approaches. No single test can accurately determine the location of ACTH excess and therefore a combination of non-invasive imaging, stimulation and suppression tests are advised. The recent advances, current utility and pitfalls of each of these tests are reviewed. If non-invasive tests fail to confidently localise the source of ACTH excess, inferior petrosal sinus sampling (IPSS) should follow. Recent advances improving the diagnostic accuracy of IPSS, such as DDAVP stimulation and simultaneous sampling for prolactin is discussed. Where ectopic ACTH production is suspected, newer nuclear medicine techniques, such as somatostatin receptor imaging that recently became available in South Africa, can be utilised. The role of nuclear medicine imaging in identifying ectopic ACTH production is discussed briefly.Keywords: ACTH, cushing’s disease, pituitary

Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism and account for less than 2% of all pituitary adenomas. In the last years, the diagnosis has been facilitated by the routine use of ultra-sensitive TSH immunometric assays. Failure to recognise the presence of a TSHoma may result in dramatic consequences, such as improper thyroid ablation that may cause the pituitary tumour volume to further expand. The diagnosis mainly rests on dynamic testing, such as T3 suppression tests and TRH, which are useful in differentiating TSHomas from the syndromes of thyroid hormone resistance. The first therapeutical approach to TSHomas is the pituitary neurosurgery. The medical treatment of TSHomas mainly rests on the administration of somatostatin analogues, such as octreotide and lanreotide, which are effective in reducing TSH secretion in more than 90% of patients with consequent normalisation of FT4 and FT3 levels and restoration of the euthyroid state.

To reevaluate the responses of thyrotropin-releasing hormone (TRH) stimulation test in baseline condition as well as after the administration of graded supraphysiological doses of liothyronine (L-T(3)) in normal subjects.To assess various parameters related to the hypothalamic-pituitary axis and peripheral tissue responses to L-T(3) in 22 normal individuals (median age: 30.5 years). Subjects were submitted to an intravenous TRH test at baseline condition and also to the oral administration of sequential and graded doses of L-T(3) (50, 100, and 200 microg/day), each given over 3 days, at an outpatient clinic. Blood samples were obtained for thyrotropin (TSH) and prolactin (PRL) at basal and then 15, 30, and 60 minutes after the TRH injection. Effects of L-T(3) administration on cholesterol, creatine kinase, retinol, ferritin, and sex hormone-binding globulin (SHBG) were also measured at basal and after the oral administration of L-T(3).TRH administration resulted in an increase of 4- to 14-fold rise in serum TSH (8.3 +/- 2.5-fold), and in a slight rise in serum PRL concentrations (3.8 +/- 1.5-fold). Administration of graded doses of triiodothyronine (T(3)) resulted in a dose-dependent suppression of TSH and PRL. Basal thyroxine-binding globulin (TBG) and cholesterol levels decreased, and ferritin and SHBG increased after L-T(3) administration, while creatine kinase and retinol did not change throughout the study. There was a positive correlation between basal TSH and TSH peak response to TRH at basal condition and after each sequential L-T(3) doses. On the other hand, TSH peak response to the TRH test did not predict cholesterol, TBG, ferritin, or SHBG values.Using the current methods on hormone and biochemical analysis, we standardized the response of many parameters to TRH stimulation test after sequential and graded T(3) suppression test in normal subjects. Our data suggest that the evaluation of the responses of the hypothalamus-pituitary axis to TRH test as well as the impact of L-T(3) on peripheral tissues were not modified by the current methods.

The clinical and endocrinological features in 106 patients (40 men, 66 women, mean age 48 +/- 14.3 years) treated between 1973 and 1993 for proven catecholamine-secreting tumours (phaeochromocytoma: n = 88, paraganglioma: n = 10, adrenal medullary hyperplasia: n = 8) were analysed. The most frequent symptoms were palpitations (68%), severe sweating (53%) and headache (42%). 10% of patients were symptom-free. 58% of patients had consistently raised blood pressure, and 20% of patients suffered paroxysmal blood pressure crises. However, 22% of patients did not have hypertension. Raised urinary catecholamines were found in more than 95% of cases; MIBG (metaiodobenzylguanidine) scintigrams were abnormal in more than 85% of cases. Patients with catecholamine-secreting tumours do not always have "classical" features. The high sensitivity of properly performed catecholamine measurement on plasma and urine has made dangerous stimulation and suppression tests obsolete.

In spite of the presence of definitive diagnostic criteria to diagnose Cushing syndrome diagnosis may become challenging. We report a young female with mild clinical features of Cushing syndrome, who had nonsuppressible oral dexamethasone suppression tests; also she had a suspicious pituitary lesion. She underwent pituitary surgery and a pituitary microadenoma (non-ACTH staining) was removed. Now she had come to us with similar complaints to those before. Again she had nonsuppressible oral dexamethasone suppression tests. As the diurnal variation of serum and salivary cortisol was maintained and urinary free cortisol was normal, further evaluation with IV dexamethasone suppression test was performed which clearly ruled out Cushing syndrome. The patient was not on any medicines known to alter dexamethasone metabolism. Fat malabsorption was also ruled out using appropriate tests. The reason for this discrepancy is thought to be altered (increased) metabolism of dexamethasone in this patient as it is widely variable in the general population.

According to the diagnostic criteria for adrenal preclinical Cushing's syndrome (PreCS) established by a group headed by the Ministry of Health, Labor and Welfare (MHLW), low- and high-dose dexamethasone suppression tests (DSTs) must be performed to prove autonomous cortisol secretion, i.e., > or =3 microg/dL serum cortisol following 1-mg DST administration, and > or =1 microg/dL serum cortisol following 8-mg DST administration. However, discrepancies have been documented in the results of low-and high-dose DSTs. We therefore investigated the validity of the DST for diagnosing PreCS by performing 1-mg and 8-mg DSTs in 39 patients with adrenal incidentaloma, but no characteristic Cushingoid symptoms. In about half of these patients (20/39, 51.3%), high-dose DST was positive but low-dose was negative, and one or more of the other abnormalities of hypothalamus-pituitary-adrenal axis dysfunction was seen in 75% of these patients. Furthermore, no significant difference in incidence of glucose intolerance and hypertension was noted in patients with positive high-dose DST and negative low-dose DST compared with patients with positive low- and high-dose DST. Under the current MHLW diagnostic criteria, patients with positive high-dose DST and negative low-dose DST are not diagnosed with PreCS, but some of these patients should be. Discrepancies in the results of low- and high-dose DSTs appear attributable to the current cutoff values, and further investigations are necessary to resolve these discrepancies.

As renin and aldosterone levels vary during the menstrual cycle, and are critical criteria for interpretation of aldosterone suppression tests to confirm or exclude primary aldosteronism, outcome of testing may vary depending on the menstrual cycle phase. We assessed the effect of timing within the menstrual cycle on levels of renin, aldosterone and female sex steroids during fludrocortisone suppression testing (FST).In 22 women undergoing FST who experienced regular menstrual cycles, renin (measured as both plasma renin activity and direct renin concentration), aldosterone (mass spectrometry) and cortisol, progesterone, oestradiol, LH and FSH (immunoassay) levels were compared, relative to phase of cycle. Aldosterone levels were compared to those in age-matched males undergoing FST.Progesterone (P0·0001) and aldosterone (P = 0·006) levels were higher in nine women (after one of 10 was excluded with anovulatory cycle) studied during the luteal phase than in the 12 studied during the follicular phase. All studied during the luteal phase had positive FST, and all three with negative FST were studied during the follicular phase. There were no significant differences in other parameters measured except FSH, which was higher (P = 0·02) during the follicular phase. Aldosterone was higher (P = 0·01) in women studied in the luteal (but not follicular) phase compared to men.The menstrual cycle may affect the outcome of FST and other suppression testing used to diagnose primary aldosteronism. Larger patient numbers and preferably restudy of the same patient in both phases should clarify this and determine the optimum time in the cycle for testing.

The aim of this study is to review the experience of the clonidine suppression test in a regional endocrine centre and to compare the diagnostic sensitivity and specificity using various previous published criteria. The design used is retrospective study. The subjects include 56 patients in whom clonidine suppression tests had been performed from 1995 to 2000: 15 with phaeochromocytoma and 41 patients in whom the diagnosis was excluded using a combination of biochemical testing, abdominal computed tomography scanning and clinical follow-up. Plasma catecholamines were measured by high pressure liquid chromatography on basal samples and at hourly intervals for 3 h after the administration of clonidine 300 μg orally and the following diagnostic criteria were applied: plasma noradrenaline+adrenaline2.96 nmol l(-1) at 3 h post-clonidine or a baseline plasma adrenaline plus noradrenaline11.82 nmol l(-1); plasma noradrenaline2.96 nmol l(-1) at 3 h post-clonidine and plasma noradrenaline2.96 nmol l(-1) and50% fall in noradrenaline at 3 h post-clonidine. The results obtained is that mean plasma noradrenaline plus adrenaline fell across the test in 40/41 patients in the non-phaeochromocytoma patients and was lowest at 3 h (basal 2.28 ± 0.14 vs 1.36 ± 0.11 nmol l(-1), P0.001). In the phaeochromocytoma group, clonidine had a variable effect on adrenaline plus noradrenaline levels with increases in 7/15. Using an abnormal result as a 3 h level of noradrenaline plus adrenaline2.96 mmol l(-1) gave a sensitivity of 93% and specificity of 95%. When a 3 h noradrenaline2.96 mmol l(-1) was used, sensitivity was 87% and specificity 95%. Using the former criteria, noradrenaline plus adrenaline2.96 mmol l(-1), 1/15 in the phaeochromocytoma group had a normal result after clonidine suppression testing. Two of 41 in the non-phaeochromocytoma group had a false-positive result. Under carefully controlled conditions, the clonidine suppression test is well tolerated, safe and accurate for use in the investigation of patients with suspected phaeochromocytoma.

Background The diagnosis of disorders of growth hormone (GH) secretion is based on the measurement of GH before and after dynamic stimulation or suppression tests. Over the years, specific cut-off values have been proposed without taking account of the considerable variation in results obtained using different methods for analysing GH. Recent publications have recommended the standardization of GH assays using IS 98/574, which is calibrated in mass and units (U). The IMMULITE range of GH assays have been recalibrated using this standard. Methods We analysed 745 samples using the current and the restandardized GH assay kits. This series of samples contained 90 stimulation tests and seven suppression tests. Results The data comparing the current and restandardized assays show a similar relationship for both basal and stimulated GH values for all IMMULITE platforms. There is a negative bias by the restandardized assay above approximately 20 μg/L. A conversion can be derived from this study which would mean that patient GH results expressed in milliunits per litre of IMMULITE in-house derived standard will be approximately three-fold of that expressed in micrograms per litre of IS 98/574. Conclusion Use of IS 98/574 offers standardized reporting in microgram per litre IS 98/574. This will permit compliance with the consensus recommendations and the development of a firm evidence base for defining decision-making GH values.

Endocrinology studies the elaboration, secretion, transportation, and action of hormones at the clinical, cellular, and molecular levels. Hormones regulate bodily functions over relatively large distances using the bloodstream or over short distances on a cell-to-cell basis. The clinical effects of hormonal dysfunction can be classified broadly into hormonal excess or deficiency. Endocrine testing utilizes the principle that suppression tests test for hormone excess, whereas stimulation tests identify hormone deficiency. These tests are conducted on the background of varying factors that modulate hormonal secretion, so results need to be cautiously interpreted. Probability theory is helpful in this situation by increasing or decreasing the likelihood of disease presence.

Numerous tests are used in clinical practice to assess the integrity of different parts of the endocrine and neuroendocrine systems. In these procedures the relationship between the inhibitory or activating effect of the diagnostic agent and the plasma concentration of the responding hormone are most often considered, without any regard to temporal aspects. As will be shown in this review, however, the time of testing represents a variable of great importance in the interpretation of the data. Furthermore, the time-related differences in the effects of the drugs used as diagnostic but also as therapeutic agents may be critical in the interpretation of both stimulation and suppression tests of endocrine and neuroendocrine functions (Touitou 1989).

With the use of a 75 g oral glucose tolerance test, both insulin release (IRG) and the degree of peripheral sensitivity (SI) were evaluated simultaneously in groups with normal (NGT) and impaired (IGT) glucose tolerance as well as NIDDM. IRG was expressed as the ratio of the area under the insulin curve to that of the glucose curve above fasting levels. The peripheral glucose uptake rate (M) during the OGTT was measured as the difference between the glucose load and the increase in the amount of glucose in the glucose space during the oral glucose tolerance test (OGTT). SI was expressed as the ratio of the metabolic clearance rate (M/mean blood glucose) to log mean serum insulin. In the non-obese groups, both mean IRG and mean SI values were decreased with an increasing degree of hyperglycemia from NGT to NIDDM. Decreased mean SI values were also found in obese subjects. IGT-subjects given 3 months of diet and exercise achieved improved SI values. A non-obese NIDDM-group had higher mean IRG and mean SI values after 6 months of treatment with glipizide. The results were comparable to data obtained with more complicated techniques, such as the insulin clamp and suppression tests, and should be easy to apply on a large scale in epidemiological studies.

We attempted to adapt an RIA method for cortisol in plasma to the analysis of “free cortisol” in urine. 3H-cortisol could be effectively extracted from urine with methylene chloride, but this solvent also extracted substances other than cortisol which were measured as “cortisol” by RIA. Urine samples which had normal cortisol measured with a competitive protein-binding assay had raised values by RIA. In an attempt to obtain the “correct” urine cortisol values for the samples, we analysed the urines using 5 commerical kits. Inspection of these results confirmed that the in-house RIA method was giving falsely high results for normal subjects, but it also showed that one kit, which was available in Canada until recently, gave spuriously high results with some urines due to interference by dexamethasone which the patients had received as part of a suppression test. We suggest that kit manufacturers should thoroughly evaluate their products prior to release, and that the evaluation should include measurements on a reasonably large and varied patient population to determine appropriate reference ranges and the response to stimulation or suppression tests.

A T4 suppression test involving 24-h thyroidal 131I uptake was carried out on patients with Graves' disease during therapy with an antithyroid drug. Thirty-three patients received propylthiouracil (PTU) for at least 1 year. Each patient was given 75 micrograms L-T3 daily for 8 days in conjunction with PTU (50 mg/day) at the time of the experiment and then the 24-h thyroidal 131I uptake (post T3 uptake was measured). Twenty-two patients had normal levels of serum T3 and T4-I before L-T3 administration and were divided into 2 groups, positive T3 suppression (post T3 uptake less than or equal to 35%, group I) and negative T3 suppression (post T3 uptake greater than 35%, group II). Eleven patients showed elevated serum T3 or T4-I concentrations before L-T3 administration (group III). The T4 suppression test was then performed on the same patients. Each patient was given 300 micrograms L-T4 daily for 8 days in conjunction with PTU and the 24-h thyroidal 131I uptake (post T4 uptake) was measured. Some patients receiving PTU (50 mg/day) were switched to MMI (5 mg/day) and the T4 suppression test was done one month later. A significant correlation between the two suppression tests during PTU therapy was observed (r = 0.961, p less than 0.01). None of the patients complained of side effects during the T4 suppression test. The mean post T4 uptake in group I was 18.8 +/- 3.3% during PTU therapy and 5.4 +/- 1.3% during MMI therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

TRH and T3 suppression tests were performed on patients (124 cases) with Graves' disease who underwent radiation therapy. TRH test was performed at 4-6 months (Group I), 6-12 months (Group II), 12-24 months (Group III) and 24-50 months (Group IV) after final radiation therapy, and T3 suppression test was performed just after each TRH test. The response to TRH test was defined as positive when the basal TSH value was less than 2.0 muU/ml and the peak value was more than 6.2 muU/ml following TRH (500 mug) injection. T3 suppression test was performed by measuring the 24-hr thyroidal uptake of radioiodine after daily administration of 75 mug of T3 for 8 days. The response was defined as positive when the value for 24-hr uptake after T3 administration was less than half of the control value. The results were as follows; 1) Among 124 patients in Group I to IV who were clinically euthyroid and whose T3-RU and T4 values were normal, compared with other groups, Group IV (2-4.2Y) showed a significantly higher percentage of positive responses to both TRH and T3 suppression tests. However, among 49 of 124 patients whose T3 was also normal, there were no significant differences between the groups. 2) The value of triiodothyronine was above the normal range in many cases up to 2 years after radiation therapy (in Group I, II, III). 3) There were no significant differences in the percentage of hyperresponses between any of the four groups. Half of the patients who showed positive responses to TRH test showed exaggerated responses. 4) In all cases when the responses to TRH and T3 suppression tests changed from negative to positive, thyroxine and triiodothyronine concentrations must be within the normal range. In particular, the major determinant seems to be the value of triiodothyronine. 5) As in more than 30% of cases TRH and T3 supression tests changed from negative to positive, thyroxine and triiodothyronine concentrations must be within the normal range. In particular, the major determinant seems to be the value of triiodothyronine. 5) As in more than 30% of cases TRH and T3 suppression tests remained negative even though their T3-RU, T4, T3, values became normal after radiation therapy, the regulation of hypothalamo-hypophyseal thyroid axis do not always return to normal even though circulating thyroidal hormone level return to an euthyroid state.

Summary. A group of 39 Nigerian infants and pre-school children with protein-energy malnutrition (PEM) have been studied. Red cell folate levels were within the range observed in 19 age-matched healthy Nigerian children. Serum vitamin B12 levels were either normal or raised. Deoxyuridine (dU) suppression tests were performed on the bone marrow cells of 30 of the patients and were abnormal in 13. It is proposed that the abnormal dU-suppressed values were not caused by vitamin B12 or folate deficiency and were probably a consequence of the protein deficiency. A few megaloblasts and several giant metamyelocytes were found in four of the cases of PEM; the remaining 35 cases had normoblastic erythropoiesis, sometimes with small to moderate numbers of giant metamyelocytes. All four marrow samples containing megaloblasts gave abnormal dU-suppressed values. However, in the marrows showing normoblastic erythropoiesis there was no correlation between the presence or absence of giant metamyelocytes and the dU-suppressed value.

A study of antithyroid drug (ATD) therapy with a mean follow-up period of 10 years (range 2-25) in 434 patients with Graves' disease has been made by linking hospital records with those of a central follow-up register. The majority (89%) were treated with carbimazole and 87% received combined therapy with triiodothyronine (T3) (73%) or thyroxine (T4) (14%). Sixty-one per cent were assessed for T3 suppression tests on completion of treatment, of whom 61% (95% CL, 55-67%) suppressed. The overall 5-year cumulative proportion developing recurrent hyperthyroidism was 54-62% with rates of 26-44% in suppressed patients and 65-79% in those not suppressed. In unsuppressed patients, most (72%) of the recurrences occurred within 1 year with only an additional 10% predicted up to 10 years. In suppressed patients 30% of recurrences occurred in the first year, 60% between 1 and 5 years and a further 10% between 5 and 10 years. Suppression with T3 is probably the best and cheapest predictor of outcome but has an accuracy of only 70% for both positive and negative tests which limits its usefulness in planning long-term follow-up and surveillance. A standard format should be adopted for the analysis and reporting of follow-up studies, based on actuarial methods of estimating the cumulative proportion with recurrences or other events, to facilitate comparisons between different centres.

Because unexplained megaloblastic erythroid maturation occurs in patients with primary refractory sideroblastic anemia (PRSA), deoxyuridine (dU) suppression tests using125 I-UdR were performed on bone marrow from five patients with PRSA. All patients had megaloblastic alterations in the marrow erythroid precursors (with normal serum folate and B12 levels) and numerous ringed sideroblasts, and most had marrow iron overload. Results of the dU suppression tests were normal in all five, both with and without incubation with pharmacologic amounts of folate, B12, and pyridoxal phosphate with or without 1-serine. Despite occasional hematologic improvement subsequent to folate, pyridoxine, or pyridoxal phosphate (PLP) administration in some patients with PRSA, normal dU suppression implies that in our group the availability of B12 and folate (and possibly PLP) was not limiting in the utilization of folate for DNA-thymine synthesis. The marrow erythroid maturation defect remains unexplained.

SummaryA total of 132 triiodothyronine suppression tests were performed using 100 μg of T3 for 7 days. Radioiodine uptake at four hours, serum thyroxine [T4(D)], T3 binding coefficient [RT3U ratio] and free thyroxine index [T4-RT3 index] were estimated before and after a course of triiodothyronine.T4(D) decreased significantly in only 38.4% of T3 suppression tests assessed as positive by the decrease in radioiodine uptake; it did not change or increased significantly in 84.7% of tests negative by radioiodine uptake.RT3U ratio showed little change in all groups. The changes in T4-RT3 index were similar to those of T4(D).The correlation of changes in T4(D) with 4 hour radioiodine uptake is poor (r = 0.34).Agreement between changes in radioiodine uptake and T4(D) was observed only in 54% of tests; between changes in uptake and T4-RT3 index in 69.4%.Estimation of serum thyroxine or free thyroxine index in the T3 suppression test cannot substitute for the radioiodine uptake for reasons which are discussed.

Triiodothyronine suppression tests with estimation of 131I uptake 20 min after i.v. injection were performed at 6-monthly intervals on 69 thyrotoxic patients treated with Carbimazol and L-triiodothyronine for 18 months. 29 patients relapsed while 40 remained euthyroid. The prognostical value of the suppression test was evaluated statistically. Uptakes under 8 per cent after 6 months' treatment suggest the patient will not relapse (prognostic sensitivity 0.8). Uptakes over 8 per cent do not select patients who relapse (prognostic specificity 0.4–0.5).

A patient with the testicular feminization syndrome underwent adrenal stimulation and suppression tests, as well as stimulation with purified human FSH prior to gonadectomy. Estrogen excretion was depressed by dexamethasone and clevated by ACTH. Purified FSH had no effect on estrogen excretion levels. After gonadectomy, preoperative urinary estrogen excretion levels were found, although the subject was not treated with exogenous steroids. Breast size, vaginal cornification, voice, and hair distribution did not change. Stimulation postoperatively with chorionic gonadotropin did not alter estrogen excretion. These data indicate that the estrogens formed in this patient are at least partly of adrenal origin.

SUMMARY Adrenocortical suppression tests, based on the fall in urinary 17-hydroxy-corticosteroid excretion during the oral administration of dexamethasone, were found to be of value in the diagnosis of Cushing's syndrome, but less useful in differentiating bilateral adrenal hyperplasia from adrenal tumour. Such tests have the disadvantage of requiring accurate urine collections and of taking several days to perform. A test is described, based on the decrease in plasma cortisol concentration during i.v. infusion of dexamethasone at a rate of 1 mg./hr. The results obtained in 12 patients with Cushing's syndrome and bilateral adrenal hyperplasia differed from those found in control subjects in that there was a delay between the start of the infusion and the fall of plasma cortisol, and the rate of fall was less rapid. The values found after 180 min., expressed either as μg./100 ml. or as a percentage of the resting level, differed significantly (P < 0·001) in the two groups. The test proved valuable as an aid to the diagnosis of Cushing's syndrome, was easy to perform, and could be completed in 3 hr. In some patients with Cushing's syndrome, the administration of synthetic glucocorticoids appeared to result in an increased urinary steroid excretion. A transient increase in plasma cortisol levels was also observed in some of these patients during the early period of dexamethasone infusion. It is thought that this finding reflects an alteration in steroid metabolism induced by dexamethasone and fluorocortisol.

Fourteen patients with Cushing's syndrome and 10 patients with a predominantly virilizing syndrome were studied and compared to a series of healthy subjects. Measurements ofurinary corticosteroids, 17-ketosteroids and aldosterone and of plasma corticosteroids were carried out while the patients were untreated, while they were receiving intramuscularinjections of ACTH over a 48-hour period, and following the withdrawal of ACTH. The results indicate that, after ACTH stimulation, the return of adrenocortical function to prestimulation levels is often delayed in patients with adrenocortical hyperfunction due to hyperplasia, as compared to normal subjects. This effect is best demonstrated by the 48-hourvalue of the plasma corticosteroids. Five-day suppression tests with 9α-fluorohydrocortisone were carried out in 10 patients. A rough correlation was observed between the responsiveness of a patient to this drug and the responsiveness of the same patient to ACTH. Initial observations with oxylone in 2 p...

Deoxyuridine (dU) suppression tests have been performed on virtually all marrow samples aspirated at this hospital over the past 12 months. Of the 110 samples studied 26 gave abnormal results, and these 26 samples came from patients deficient in either vitamin B(12) or folate. The dU suppression test was found to be of particular value in the diagnosis of vitamin B(12) or folate deficiency in non-anaemic patients with macrocytosis and equivocal changes in marrow morphology and in patients in whom the serum vitamin B(12) or red cell folate levels were within the normal range.

The decrease of insulin secretion in normal subjects in response to hypoglycaemia provides the basis for diagnostic suppression tests for insulinomas. Sixteen out of twenty patients with insulinomas had hypoglycaemia after an overnight fast, and an insulinoma could be diagnosed when the plasma-insulin levels were inordinately high in relation to the hypoglycaemia. Fish insulin was used to induce hypoglycaemia in twelve patients with insulinomas, four of whom had normal basal glucose levels after an overnight fast, and in all subjects suppression of endogenous insulin secretion was impaired. This dynamic suppression test provides a means of diagnosing or excluding an insulinoma as a cause of suspected hypoglycaemic attacks.

In order to examine the dexamethasone suppressibility of plasma pregnenolone, 9 a.m. and overnight suppression tests were performed in normal adult subjects and plasma pregnenolone levels were radioimmunoassayed. The results were as follows: 1) In the 9 a.m. test, plasma pregnenolone was suppressed to the lowest level at the time between 30 min and 2 hr after dexamethasone; 2) there was no significant difference in dexamethasone suppressibility of plasma pregnenolone between the 9 a.m. test and overnight test; 3) there was no significant difference from each other among the plasma pregnenolone levels after dexamethasone administration (0.5 mg to 3 mg) in both tests; 4) after dexamethasone administration, plasma pregnenolone was not suppressed below 40% of the basal level in both tests; 5) discussions were made about the results, comparing with those of the suppressibility of cortisol which were previously reported from this laboratory.

We describe the sequential results of C-peptide suppression tests during follow-up of a patient with a malignant insulinoma who underwent surgery at the time of diagnosis and had a seven-year remission before relapse. In addition, we document the successful outcome of a second surgical procedure for resection of metastases following relapse

A thyroid suppression test is suggested which relies on the change in concentration of serum thyroxine as the index of thyroid response to the administration of triiodothyronine. The test has been carried out in 16 healthy volunteers and in 27 patients referred for routine suppression tests. This index appears to be sensitive and safe and results in a reduction in the required dosage of triiodothyronine. The test can be carried out in fewer patient-visits than the commonly used suppression test; moreover, in remote areas the patient need not attend the specialist centre because the course of triiodothyronine can be given (and the serum samples obtained) locally, the samples then being sent to the appropriate laboratory for assay.

In normal volunteers infusion of parathyroid extract raised plasma 1,25-dihydroxyvitamin D (1,25-[OH] 2 D) levels by 80% (peak 8-40 h after infusion) without producing any significant change in plasma calcium, phosphate, or magnesium. An oral calcium load suppressed plasma 1,25-(OH) 2 D to 63% of control values within 48-72 h. These responses will be useful in the diagnosis and management of disturbances of calcium and mineral metabolism in which vitamin D metabolism is abnormal.

SUMMARY Regular measurement of thyroidal radioiodine uptake has been widely used as a means of monitoring continued extrapituitary stimulation of the thyroid during the treatment of thyrotoxicosis with carbimazole and triiodothyronine (T3). However, it is unclear to what extent the serum T3 level may vary at the time of testing, nor what effect this might have on the uptake of radioiodine. Two studies have been undertaken. In the first, serum T3 levels in twenty-four thyrotoxic patients were measured at intervals during an 18-month course of carbimazole combined with T3, 20 μg qid. Considerable variations in the highest and lowest levels of serum T3 were found both between and within individuals. The second study was on twenty-three thyrotoxic patients thought to be entering remission because the iodine uptake after 5 months of drug treatment had fallen to less than 50% of the pretreatment value (suppressors). The changes in uptake of radioiodine after 5 and then 6 months of treatment were compared in seven patients, who received carbimazole and T3 throughout, with the corresponding changes in the remaining sixteen patients, whose T3 alone was withdrawn prior to the uptake test at month 6. The mean degree of suppression remained unchanged by month 6 in the first group. In the second group, however, the mean uptake rose significantly, and nine of the sixteen patients would have been classified as non-suppressors at the sixth month (i.e. uptake greater than 50% the pretreatment value) had their failure to maintain high serum levels of T3 gone undetected. The first study indicated this could well happen in routine circumstances, and it is suggested that the reliability of suppression tests be checked with simultaneous measurement of serum T3.

Forty-seven mineral oils were tested for their ability to induce sebaceous gland suppression in female C3H/HeN or CF1 mice. Six groups of five mice were treated with zero, one, two, three, four or six epidermal applications of one or more of three volumes (0.2, 0.1 or 0.05 ml) of the test substance. The sebaceous gland suppression indices were calculated from the total numbers of sebaceous glands and hair follicles in nine sections of treated skin from each mouse. Suppression curves were drawn by plotting the mean suppression indices against the number of applications of each oil sample. The suppression curves were compared with the cutaneous carcinogenic potentials of these mineral oils, assessed by long-term skin bioassays. All the carcinogenic oil samples induced suppression of sebaceous glands. The non-carcinogenic samples had no significant suppressant activity. There was a correlation between cutaneous carcinogenic activity and suppressant potential for all tested samples. Results of the suppression tests considered, together with the kinematic viscosities of the test substances, enabled accurate prediction of their cutaneous carcinogenic potential.

The relationship of Graves' disease and heredity was studied in 97 clinically and biochemically euthyroid relatives (resin T3 uptake and serum T3, T4, and TSH within normal ranges) who had more than two thyrotoxic relatives within the second degree relationship. TRH tests were preformed in all 97 cases. In 56 of the 97, T3 suppression tests were performed shortly after the TRH test. Results revealed that 29 of the 97 (29.9%) showed an abnormal response to TRH. fourteen of these (14.4%) revealed no response or a hyporesponse, and 15 (15.5%) revealed a hyperresponse to TRH. Four of 56 (7.1%) were T3 nonsuppressible. Seven individuals who showed no response or a hyporesponse to TRH consisted of 2 nonsuppressible and 5 suppressible subjects. In 14 non- or hyporesponsive cases, serum T3 (1.51 +/- 0.05 ng/ml; mean +/- SE) and T4 (9.91 +/- 0.31 micrograms/dl) were significantly higher compared with those of normal responders (1.30 +/- 0.04 ng/ml, 8.57 +/- 0.21 micrograms/dl; P less than 0.001) or hyperresponders (1.16 +/- 0.06 ng/ml, 7.77 +/- 0.63 micrograms/dl; P less than 0.01). There was no correlation between TRH responsiveness and T3 suppressibility. A relatively high occurrence of thyroglobulin and microsomal antibodies was observed, further suggesting a hereditary predisposition. The findings indicate that even in euthyroid relatives with a family history of Graves' disease who have no clinical or biochemical abnormalities of thyroid dysfunction, many have abnormalities in TRH responsiveness, T3 suppressibility, and thyroidal antibodies.

Fourteen depressed patients were given the dexamethasone and ACTH suppression tests. The results of 71% agreed, suggesting that in a subgroup of depressed patients dexamethasone resistance reflects a central rather than peripheral dysfunction of the hypothalamic-pituitary-adrenal axis.

We have used a nominal 10 mc I 132 generator, supplied by the Brookhaven National Laboratory, in a set of diagnostic studies of the thyroid gland. We have found that a clear distinction between hyper- and hypo- or euthyroidism can be observed 100 min after administration of a diagnostic dose of I 132 . The 2-hr uptake of I 132 , together with the 2-hr neck/thigh ratio, are convenient tests for a quick diagnosis of hyper- and hypo- or euthyroidism. Tests using I 132 can be repeated frequently, since 24 hr after ingestion there is but 1/1000 of the dose remaining in the patient. Suppression tests using tri-iodothyronine or thiocyanate and stimulation tests with TSH or pituitary gland extracts present results comparable to those obtained with I 131 . The I 132 generator permits the use of this isotope in places distant from the production site and in quantities sufficient for at least three weeks.

Seventy-six thyrotoxic patients were studied by means of thyroid suppression tests (using thyroxine or triiodothyronine) after treatment with radioactive iodine. They were grouped according to the various intervals after therapy. Significant suppression of thyroid function was demonstrated as early as six weeks after treatment with radioiodine. There was close correlation between the degree of suppression achieved and the final clinical status of the patient. Suppressibility, absent in the thyrotoxic state, returns when the patient is rendered euthyroid.

Five urinary androgens were gas chromatographically estimated in 5 girls (aged 12 1 2 to 16 yr.) with gonadal dysgenesis during an investigation on the effects of stimulation-suppression tests with adrenocorticotrophic hormone, dexamethasone and human chorionic gonadotrophins. Four girls had 45/XO karyotype and one had XX/XY/XΛ The results revealed that in most patients the source of the androgens, including testosterone, was the adrenal. An exaggerated response to ACTH seen in the patients may be due to a compensatory mechanism in the adrenals, which indicates an overall integration of androgen production from adrenals and gonads in the females.

Patients with myxedema and high thyrotropin (h-TSH) levels were given levothyroxine (l-T4) orally in doses increasing stepwise from 0.025 to 0.2 mg per day at 3-week intervals. The serum h-TSH response was similar regardless of etiology of the myxedema. In all but one patient, h-TSH levels were suppressed to normal at 0.2 mg per day, but at lower doses, many patients still had increased h-TSH levels when total and free T4 levels were normal. h-TSH was correlated with dose of T4 (r equals -0.99), total T4 (r equals -0.99), and free T4 (r equals -1.0). Five patients were given levo-tri-iodothyronine (l-T3) orally in doses increasing each week by 25 μg daily to 100 μg per day; serum h-TSH levels became normal in all patients with 100 μg per day but not with 75 μg per day. For T3 suppression tests, 75 μg per day is not sufficient for routine use. Serum h-TSH levels appear to offer the best means of diagnosing hypothyroidism and assessing adequacy of thyroid-hormone therapy.

Fifty-three thyroid suppression tests were carried out at the end of a year of treatment of hyperthyroidism with antithyroid drugs. Two to 7 years later (average 47 months), 27 patients were well and 26 patients had relapsed or had experienced a recurrence within periods ranging from a few days to 69 months (average 7 months) after antithyroid drugs were discontinued. The average value of 24-hr 131I uptake after the test for those who remained well was 23%, in contrast to 58% for those in whom hyperthyroidism recurred (p

Excerpt To the editor: In their article "Evaluation of Stimulation and Suppression Tests in the Etiological Diagnosis of Cushing's Syndrome" (Ann Intern Med71:941-949, 1969) the authors have includ...

An evaluation of dexamethasone suppression, metyrapone and adrenocorticotrophic hormone (ACTH) stimulation, plasma radioimmunoassayable ACTH, and retrograde adrenal venography in the diffe...