Various chemotherapeutic modalities have been tried in the treatment of patients with malignant glucagonomas. Promising results have been reported after drug treatment with dimethyltriazenoimidazole carboxamide (DTIC). We present a patient with a metastasizing pancreatic glucagonoma, in whom treatment with neither DTIC nor with the combination of streptozotocin and 5-fluorouracil resulted in any noticeable improvement.

OBJECTIVEInsulin resistance is a frequent consequence of GH replacement therapy but patients on GH replacement therapy often also have replacement of other hormone deficiencies which theoretically could modify the metabolic effects of GH. In particular, cortisol replacement if given in supra physiologic doses immediately before the evaluation of insulin sensitivity could influence insulin sensitivity. The aim of this study was thus to evaluate the effect of morning cortisol replacement given prior to a euglycaemic clamp combined with infusion of [3-(3)H]glucose and indirect calorimetry on glucose and lipid metabolism.METHODSTen GH/ACTH-deficient adults received, in a double-blind manner, either cortisol (A) or placebo (B) before the clamp whereas five GH-deficient-ACTH-sufficient adults participated in a control (C) clamp experiment. All subjects received GH replacement therapy.RESULTSSerum cortisol levels were significantly higher after cortisol than after placebo (324+/-156 vs 132+/-136 mmol/l; P=0.006) and similar to controls (177+/-104 mmol/l). As a measure of the biological effect of cortisol, eosinophil leukocyte counts in peripheral blood decreased (164+/-91 x 10(9)/l vs 216+/-94 x 10(9)/l; P=0.04). Cortisol replacement had no significant effect on insulin-stimulated glucose uptake (11.8+/-1.8 vs 13.2+/-3.9 micromol/kg min), either on glucose oxidation or on glucose storage. There was also no significant effect of cortisol on fasting endogenous glucose production and no effect was seen on serum free fatty acid concentrations.CONCLUSIONAdministration of cortisol in the morning before a clamp cannot explain the insulin resistance seen with GH replacement therapy.

OBJECTIVE: Previous studies evaluating the lipolytic effect of GH have in general been performed in subjects on chronic GH therapy. In this study we assessed the lipolytic effect of GH in previously untreated patients and examined whether the negative effect of enhanced lipolysis on glucose metabolism could be counteracted by acute antilipolysis achieved with acipimox. METHODS: Ten GH-deficient (GHD) adults participated in four experiments each, during which they received in a double-blind manner: placebo (A); GH (0.88+/-0.13 mg) (B); GH+acipimox 250 mg b.i.d. (C); and acipimox b.i.d. (no GH) (D), where GH was given the night before a 2 h euglycemic, hyperinsulinemic clamp combined with infusion of [3-(3)H]glucose and indirect calorimetry. RESULTS: GH increased basal free fatty acid (FFA) levels by 74% (P=0.0051) and insulin levels by 93% (P=0.0051). This resulted in a non-significant decrease in insulin-stimulated glucose uptakes (16.61+/-8.03 vs 12.74+/-5.50 micromol/kg per min (s.d.), P=0.07 for A vs B). The rates of insulin-stimulated glucose uptake correlated negatively with the FFA concentrations (r=-0.638, P<0.0001). However, acipimox caused a significant improvement in insulin-stimulated glucose uptake in the GH-treated patients (17.35+/-5.65 vs 12.74+/-5.50 micromol/kg per min, P=0.012 for C vs B). The acipimox-induced enhancement of insulin-stimulated glucose uptake was mainly due to an enhanced rate of glucose oxidation (8.32+/-3.00 vs 5.88+/-2.39 micromol/kg per min, P=0.07 for C vs B). The enhanced rates of glucose oxidation induced by acipimox correlated negatively with the rate of lipid oxidation in GH-treated subjects both in basal (r=-0.867, P=0.0093) and during insulin-stimulated (r=-0.927, P=0.0054) conditions. GH did not significantly impair non-oxidative glucose metabolism (6.86+/-5.22 vs 8.67+/-6.65 micromol/kg per min, P=NS for B vs A). The fasting rate of endogenous glucose production was unaffected by GH and acipimox administration (10.99+/-1.98 vs 11.73+/-2.38 micromol/kg per min, P=NS for B vs A and 11.55+/-2.7 vs 10.99+/-1.98 micromol/kg per min, P=NS for C vs B). On the other hand, acipimox alone improved glucose uptake in the untreated GHD patients (24.14+/-8.74 vs 16.61+/-8.03 micromol/kg per min, P=0.0077 for D vs A) and this was again due to enhanced fasting (7.90+/-2.68 vs 5.16+/-2.28 micromol/kg per min, P=0.01 for D vs A) and insulin-stimulated (9.78+/-3.68 vs 7.95+/-2.64 micromol/kg per min, P=0.07 for D vs A) glucose oxidation. CONCLUSION: The study of acute administration of GH to previously untreated GHD patients provides compelling evidence that (i) GH-induced insulin resistance is mainly due to induction of lipolysis by GH; and (ii) inhibition of lipolysis can prevent the deterioration of insulin sensitivity. The question remains whether GH replacement therapy should, at least at the beginning of therapy, be combined with means to prevent an excessive stimulation of lipolysis by GH.

The effects of GH replacement therapy on energy metabolism are still uncertain, and long-term benefits of increased muscle mass are thought to outweigh short-term negative metabolic effects. This study was designed to address this issue by examining both short-term (1 wk) and long-term (6 months) effects of a low-dose (9.6 micro g/kg body weight.d) GH replacement therapy or placebo on whole-body glucose and lipid metabolism (oral glucose tolerance test and euglycemic hyperinsulinemic clamp combined with indirect calorimetry and infusion of 3-[(3)H]glucose) and on muscle composition and muscle enzymes/metabolites, as determined from biopsies obtained at the end of the clamp in 19 GH-deficient adult subjects. GH therapy resulted in impaired insulin-stimulated glucose uptake at 1 wk (-52%; P = 0.008) and 6 months (-39%; P = 0.008), which correlated with deterioration of glucose tolerance (r = -0.481; P = 0.003). The decrease in glucose uptake was associated with an increase in lipid oxidation at 1 wk (60%; P = 0.008) and 6 months (60%; P = 0.008) and a concomitant decrease in glucose oxidation. The deterioration of glucose metabolism during GH therapy also correlated with the enhanced rate of lipid oxidation (r = -0.508; P = 0.0002). In addition, there was a shift toward more glycolytic type II fibers during GH therapy. In conclusion, replacement therapy with a low-dose GH in GH-deficient adult subjects is associated with a sustained deterioration of glucose metabolism as a consequence of the lipolytic effect of GH, resulting in enhanced oxidation of lipid substrates. Also, a shift toward more insulin-resistant type II X fibers is seen in muscle. Glucose metabolism should be carefully monitored during long-term GH replacement therapy.

Objective. To determine the diagnostic value of metaiodobenzylguanidine (MIBG) scintigraphy compared with computed tomography (CT) for the localization of phaeochromocytomas in clinical practice.Design. Retrospective comparison between MIBG scintigrams and CT for localization of phaeochromocytomas in all patients successively examined with MIBG scintigraphy in Malmo from 1984 until January 1997.Setting. Malmo University Hospital, Sweden.Subjects. Sixty-four patients with clinically suspected phaeochromocytomas.Main outcome measures. MIBG scintigrams and CTs classified as positive or negative based on original interpretations (primary evaluation) and in a secondary evaluation by one blinded examiner are assessed through histological confirmation or clinical rule out of phaeochromocytomas.Results. Twenty-five patients had surgically removed phaeochromocytomas. The remaining 39 patients had no proof of phaeochromocytomas. In the secondary evaluation, sensitivity for MIBG scintigraphy was 88%, (22/25) and for CT was 100%, (25/25). The specificity for MIBG scintigraphy was 89%, (35/39) but only 50%, for CT (18/36). Two out of a total of six extra-adrenal tumours were amongst the false-negative MIBG scintigrams.Conclusions. MIBG scintigraphy for the localization of phaeochromocytomas is superior to CT as far as specificity, whereas CT has a higher sensitivity. After biochemical diagnosis. CT will detect most phaeochromocytomas. MIBG scintigraphy can be of value in patients who show inconclusive results with biochemical testing and CT.

To test the hypothesis that GH-induced insulin resistance is mediated by an increase in FFA levels we assessed insulin sensitivity after inhibiting the increase in FFA by a nicotine acid derivative, Acipimox, in nine GH-deficient adults receiving GH replacement therapy. The patients received in a double blind fashion either Acipimox (500 mg) or placebo before a 2-h euglycemic (plasma glucose, 5.5 +/- 0.2 mmol/liter) hyperinsulinemic (serum insulin, 28.7 +/- 6.3 mU/liter) clamp in combination with indirect calorimetry and infusion of [3-(3)H]glucose. Acipimox decreased fasting FFA by 88% (P = 0.012) and basal lipid oxidation by 39% (P = 0.015) compared with placebo. In addition, the insulin-stimulated lipid oxidation was 31% (P = 0.0077) lower during Acipimox than during placebo. Acipimox increased insulin-stimulated total glucose uptake by 36% (P = 0.021) compared with placebo, which mainly was due to a 47% (P = 0.015) increase in glucose oxidation. GH induced insulin resistance is partially prevented by inhibition of lipolysis by Acipimox.

OBJECTIVE:To investigate the effect of GH on myosin heavy chain (MHC) isoform composition, physical fitness and body composition in GH-deficient (GHD) patients.DESIGN:Twenty-two GHD patients were randomized in a double blind manner and half were treated with recombinant human GH (rhGH) and half were treated with placebo for 6 months. Twelve age-matched controls were also included in the study.METHODS:MHC isoform composition in biopsies obtained from the vastus lateralis muscle was determined using SDS-PAGE. Physical fitness was determined on a bicycle ergometer and body composition was determined using bioelectrical impedance analysis.RESULTS:More MHC IIX (28.9 +/- 4.1% and 10.0 +/- 3.1% in GHD and controls respectively (means +/- S.E.M.)) and less MHC I (36.2 +/- 2.4% and 51.7 +/- 3.9% in GHD and controls respectively (means +/- S.E.M.)) were present in the GHD patients compared with the controls. No significant difference in the amount of MHC IIA was detected. Linear regression was used to determine the relationship between variables. There were no significant relationships between the concentration of insulin-like growth factor-I (IGF-I) or the body composition and the MHC composition. Maximal oxygen uptake (VO(2)max) per kg body weight (BW) (litres/min per kg) correlated significantly with the amount of MHC I (r=0.60) and MHC IIX (r=-0.72) but not with the amount of MHC IIA (r=0.35). Treatment of GHD patients with rhGH for 6 months increased the concentration of IGF-I, lean body mass and decreased fat mass but had no effect on MHC composition and physical fitness.CONCLUSIONS:We conclude that a major part of the differences in MHC composition between GHD patients and age-matched controls can be explained by variation in physical fitness. The severity of the GHD and the body composition does not seem to be important for the MHC composition. Furthermore, treatment with GH for 6 months does not affect MHC composition in GHD patients.

The aim of the present trial was to study the individual responsiveness to GH treatment in terms of body composition and to search for possible predictors of the response in GH-deficient adults. Sixty-eight patients (44 men and 24 women) with a mean age of 44.3 (1.2) yr and verified GH deficiency participated in a 2-phase treatment trial with an initial randomized, double blind, placebo-controlled, 6-month period, followed by an open treatment period, thereby ensuring all patients 12 months of GH treatment. Recombinant human GH was administered sc daily at bedtime, with a target dose of 12 micrograms/kg x day. GHBP was measured by ligand-mediated immunofunctional assay, and serum insulin-like growth factor I (IGF-I) was determined by RIA after acid-ethanol extraction, using a truncated IGF-I analog as the radioligand. Lean body mass (LBM) and body fat (BF) were determined by dual energy x-ray absorptiometry, and total body water (TBW) was determined by bioelectrical impedance. During the placebo control period, serum IGF-I,LBM, and TBW increased (P < 0.001), whereas BF decreased (P < 0.001) and serum GHBP was unchanged in the group treated with GH compared with the patients treated with placebo. After 12 months of GH treatment, the individual changes in BF ranged from -12.5 to 4.3 kg and from -4.5 to 10.1 kg in LBM. Age (P < 0.05) and baseline GHBP level (P < 0.01) were inversely correlated with the increase in LBM. The GH-induced increment in IGF-I and TBW was greater in men than in women (P < 0.01), whereas the decreases in BF were similar in men and women. This trial demonstrates the variability in responsiveness to GH administration in GH-deficient adults. The best response to GH was obtained in younger patients with low GHBP levels. Furthermore, men responded better than women.

Degerblad M, Bengtsson B-Å, Bramnert M, Johnell O, Manhem P, Rosén T, Thorén M. Reduced bone mineral density in adults with growth hormone (GH) deficiency: increased bone turnover during 12 months of GH substitution therapy. Eur J Endocrinol 1995;133:180–8. ISSN 0804–4643 To evaluate the consequences of growth hormone (GH) deficiency on bone mineral density and to evaluate the effects of GH substitution therapy, 68 adults (25 females and 43 males) aged 22–61 (mean 44.2 ± 1.2) years with GH deficiency (GHD) were studied. Fifty-eight patients had panhypopituitarism, three had isolated GHD and in seven patients at least one additional pituitary function was affected. Twenty-one patients had childhood onset GHD. The patients were randomized to receive either GH in daily injections (0.125 IU · kg−1 · week−1 for the first 4 weeks and subsequently 0.25 IU · kg−1 · week−1) or placebo for 6 months. The trial continued as an open study with GH treatment for 6 or 12 months, with data presented as compiled data of 12 months of GH treatment in 64 patients. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry and bone turnover was assessed by serum markers of bone metabolism (osteocalcin, procollagen I peptide, crosslinked telopeptide of type I collagen and alkaline phosphatase activity). In women with adult onset GHD (N = 19) and in men with childhood onset GHD (N = 15), total body, spine and hip BMD was significantly reduced at baseline compared to Swedish age- and sex-matched control material. In men with adult onset of GHD (N = 28), BMD did not differ from male controls. During the placebocontrolled period, GH induced decreased total body and spine BMD, probably due to an expansion of the remodelling space, whereas all serum markers of bone turnover increased. Compiled GH data showed similar results after 6 months of treatment. After 12 months of GH treatment, BMD did not differ from basal values except for total body BMD, which was lower, whereas the serum markers of bone metabolism were still increased as compared to basal values. Two-thirds of the patients experienced fluid retention with peripheral oedema and arthralgias on the higher GH dosage. One obese patient developed non-insulin-dependent diabetes mellitus and was withdrawn from the study. These results demonstrate that GHD has negative effects on BMD and that GH substitution induces increased bone turnover. Continued long-term observations will reveal if there is a positive effect of GH substitution on bone mass in the adult GHD patient. Marie Degerblad, Department of Endocrinology and Diabetology, Karolinska Hospital, S-17176 Stockholm, Sweden

Cardiac pheochromocytoma is a rare tumour andmay be difficult to localize. We present a 32-year-old male with a cardiac pheochromocytoma that was successfully resected. An initial unenhanced CT did not reveal the tumour. MIBG-scintigraphy indicated the location, but to get full information, a dynamic contrast-enhanced CT of the chest during adequate alpha and beta blockade was essential. ECG-gated MRI gave further information about the anatomical details.

OBJECTIVE AND PATIENTS To further explore the difference in plasma noradrenaline in normotensive and hypertensive hypothyroid patients we have investigated the presser response to exogenous noradrenaline in 11 normotensive and five hypertensive patients with primary hypothyroidism before and after thyroxine replacement. Seven healthy subjects served as controls.DESIGN The patients were studied under metabolic ward conditions and received a Na+ and K+ defined diet for 4 days. The controls received the same diet on an ambulatory basis for 3 days and were admitted to the ward in the evening on the third day. In the morning of day 4 a graded noradrenaline infusion was given. When the increase in systolic blood pressure in two consecutive registrations was at least 20 mmHg as compared to basal values the noradrenaline infusion was stopped. The dose required to increase systolic blood pressure by 20 mmHg (I-20) was determined.RESULTS During hypothyroidism the I-20 was 120 ng/kg BW/min in normotensive patients and 39 in hypertensive patients as compared to 62 in controls. The 120 was higher in normotensives as compared to hypertensives (P=0.041). The I-20 was not different in hypertensives as compared to controls. When the patients had become euthyroid I-20 decreased to 51 ng/kg BW/min (P=0.04) in the normotensives, but remained unchanged in the hypertensives. There was no difference in I-20 between normotensive and hypertensive patients in the euthyroid state, or when compared to controls.CONCLUSION The presser response to noradrenaline was decreased in normotensive hypothyroid as compared to hypertensive hypothyroid patients, indicating a decreased peripheral sensitivity to noradrenaline in normotensive hypothyroid patients. Following thyroxine replacement the decreased response became normal.

The purpose of the study was to measure the urinary excretion of N-acetyl-beta-glucosaminidase (U-NAG) in patients suspected of having renovascular hypertension and to compare the enzyme excretion before and after active intervention with operation or percutaneous transluminal renal angioplasty (PTRA). Eighty-one patients with severe, therapy-resistant hypertension were examined with regard to renal artery stenosis (RAS). At least one significant renal artery stenosis was found in 61 patients, whilst the remaining 20 patients were classified as having essential hypertension. Enzyme levels were found to be significantly higher in RAS patients as compared with patients with severe hypertension lacking significant renal artery stenosis, 0. 66 (0.41-0.9 1, median value, lst and 3rd quartiles) versus 0.35 (0.27-0.54), P < 0.01. Both groups of patients had significantly higher U-NAG values than a healthy reference population (0.2, 0.13-0.27; P < 0.01). Forty of the RAS patients were randomized to surgery or PTRA and followed prospectively for 2 years. After either renal vascular surgery or PTRA a significant rise in U-NAG excretion was observed 7-10 days after treatment. Urinary NAG excretion remained elevated during long-term follow-up. It is suggested that U-NAG should be determined in patients with therapy-resistant hypertension with suspicion of renal artery stenosis.

The purpose of this prospective randomized study was to compare percutaneous transluminal renal angioplasty (PTRA) and operation as initial therapy with regard to technical results, primary and secondary patency, and effects on blood pressure and renal function in patients with atherosclerotic unilateral renal artery stenosis.Fifty-eight patients who did not have diabetes, who were less than 70 years of age, and who had severe hypertension and significant stenosis were randomized to receive PTRA or operation. Angiography was performed 10 days, 1 year, and 2 years after treatment to verify patency, and blood pressure and renal function were simultaneously evaluated.Technically, PTRA was successful in 83% and operation in 97% of patients. The primary patency rate after 24 months was 75% in the PTRA group and 96% in the operative group in technically successful cases. The secondary patency rate in the PTRA group was 90% and in the surgical group 97%. To achieve these results four patients in the PTRA group required operation, and one patient in the surgical group required PTRA. Hypertension was cured or improved after additional treatment in 90% of the patients after PTRA and 86% after operation. The corresponding figures for improved or unchanged renal function were 83% and 72%, respectively. After additional treatment, effects on blood pressure and renal function did not differ. Seventeen percent of the patients treated with PTRA required surgical intervention.PTRA is recommended as first choice of therapy for atherosclerotic renal artery stenosis causing renovascular hypertension if combined with intensive follow-up and aggressive reintervention.

The use of venous plasma noradrenaline levels as a marker of general sympathetic tone has been questioned as changes in local sympathetic activity may influence the venous levels. To compare arterial and venous plasma noradrenaline levels in patients with primary hypothyroidism, arterial and venous blood were sampled during strictly standardized conditions during hypothyroid and euthyroid states. The patients were hospitalized for 5 days at a metabolic ward on a standardized sodium and potassium intake. On the fourth day catheters were positioned in the axillary artery and vein. Blood samples were drawn simultaneously for noradrenaline and adrenaline determinations during resting conditions. The arterial and venous plasma noradrenaline levels did not differ significantly, neither during hypothyroidism nor during euthyroidism. The arteriovenous difference in plasma adrenaline was similar during hypothyroidism compared to euthyroidism, indicating similar peripheral extraction rate of catecholamines during hypothyroidism as compared to euthyroidism. During hypothyroidism venous and arterial noradrenaline were significantly higher as compared to euthyroidism. In conclusion, there is no difference between arterial and venous noradrenaline levels either in the hypothyroid or the euthyroid state, and the peripheral extraction rate of plasma noradrenaline seems to be similar in hypothyroidism and euthyroidism. The local contribution of noradrenaline from the arm, reflecting local sympathetic nervous activity, is limited during resting conditions. In hypothyroid patients plasma noradrenaline levels are increased as compared to the euthyroid state, indicating increased general sympathetic activity in hypothyroidism.

Plasma concentrations of adrenaline, noradrenaline, aldosterone and plasma renin activity were determined in a selected group of 80- year- old men (N=41) in good health without clinical signs of cardiovascular disease, and were compared to levels in young healthy males (N=20, 24–28 years). Plasma adrenaline and noradrenaline concentrations were higher (0.24 median; 25th–75th percentiles 0.16–0.34 nmol/L vs 0.15; 0.11–0.18 nmol/L, p<0.01 and 2.22; 1.58–3.27 nmol/L vs 1.15; 1.00–1.74 nmol/L, p<0.001), and plasma renin activity and plasma aldosterone concentration were lower in the old than in the young men (0.65; 0.35–1.04 μg/L/1h vs 2.09; 1.23–2.41 μg/L/1h, p<0.001 and 0.12; 0.09–0.19 nmol/L vs 0.38; 0.28–0.54 nmol/L, p<0.001). In conclusion, increased plasma concentrations of catecholamines and decreased plasma concentration of aldosterone and plasma renin activity in old men, as compared to young men, must be considered when interpreting data of these hormones in elderly men. (Aging Clin. Exp. Res. 4: 341–345, 1992)

Plasma neuropeptide Y (NPY), plasma galanin and plasma catecholamines were determined before and during an ergometer exercise test in 11 type 1 diabetic patients (age 19–36 years, mean 30; duration of diabetes 2–18 years, mean 9) with autonomic dysfunction and in 13 age-matched healthy controls (age 24–36 years, mean 29). Before exercise, plasma NPY (100 ± 6 pmol/l vs 144 ± 7 pmol/l; P < 0.001) and plasma galanin (54 ± 3 pmol/l vs 77 ± 5 pmol/l; P < 0.005) were significantly lower in patients than in controls. During exercise, plasma NPY, plasma adrenaline, and plasma noradrenaline increased in patients and controls while galanin only increased in patients. Since there was a direct correlation between plasma NPY before exercise and the increment (Δ80%) in noradrenaline during exercise (r = 0.54; P < 0.01), it is suggested that plasma NPY determined in the basal situation may be a useful marker of sympathetic nerve failure in diabetic patients.

To evaluate the renin-angiotensin-aldosterone system in relation to circulatory catecholamines, we determined renin activity, angiotensin II, aldosterone, adrenaline, and noradrenaline in plasma before and during a submaximal bicycle exercise test in 23 Type 1 (insulin-dependent) diabetic patients (aged 19–57 years, mean 37; duration of diabetes 2–32 years, mean 16), 17 with signs of cardiac autonomic neuropathy, and in 18 healthy non-diabetic subjects (aged 24–41 years, mean 29). At rest, Type 1 diabetic patients showed significantly lower aldosterone values than control subjects (0.14±0.02 nmol/l and 0.22±0.02 nmol/l; p<0.01) while renin activity (1.0±0.1 nmol·l−1·h−1 and 0.9±0.1 nmol·l−1·h−1) and angiotensin II (14±1 nmol/l and 18±2 nmol/l) did not differ significantly between patients and control subjects. During exercise, increments (increase from the resting value to the value at 80% of maximal working capacity) in renin (1.5±0.4 nmol·l−1·h−1 and 3.7±0.5 nmol·l−1 ·h−1; p<0.001), angiotensin II (28±8 nmol/l and 60±8 nmol/l; p<0.01), aldosterone (0.16±0.04 nmol/l and 0.25±0.05 nmol/l; p<0.05), adrenaline (1.96±0.49 nmol/l and 2.92±0.51 nmol/l; ps<0.05), and noradrenaline (12.01±1.25 nmol/l and 18.74±1.45 nmol/l; p<0.01) were significantly lower in the patients than in control subjects. There was no difference in the renin-angiotensin-aldosterone response to exercise between patients with and without cardiac autonomic neuropathy but the impaired catecholamine reaction was confined to patients with cardiac autonomic neuropathy. In conclusion, Type 1 diabetic patients demonstrated low resting plasma aldosterone and reduced increments in renin activity, angiotensin II, aldosterone, and catecholamines during exercise. The low aldosterone values might be related to dysfunction of adrenal zona glomerulosa cells while it is unlikely that the reduced response to exercise of the renin-angiotensin-aldosterone system simply reflects sympathetic nerve failure.

In this prospective study, 25 consecutive patients with untreated primary hypothyroidism were tested with a highly sensitive perimetric technique, since a high prevalence of visual field defects has been described in this condition. All patients had clinical hypothyroidism, a serum TSH value greater than 20 mU/l (reference range 0.4-4.0) and decreased/low normal serum total T4 concentration. Visual fields were tested with fully automated threshold-measuring computerized perimetry of the central 30 degrees field. Interpretation of fields included computer-assisted analysis provided by a perimetric statistical programme package. In 23 patients, conventional inspection and computer-assisted analysis showed no visual field defects. Two patients were excluded from the latter analysis: one patient who did not respond adequately at computerized perimetry and in whom manual field tests were entirely normal: one patient who had low sensitivity values in the uppermost parts of both visual fields owing to markedly swollen upper eye lids. In conclusion, although pituitary hyperplasia has been well documented in primary hypothyroidism, the present prospective study clearly indicates that visual field defects are not a common finding in patients with this disease.