Cystic islet cell tumors of the pancreas.
Explore the source record for details and available documents.
Adenoma, Islet Cell↗
Biomedical subjects
G M Besser
Publications and source records attributed to G M Besser.
Double modulation of 5-fluorouracil with interferon alpha-2a and high-dose leucovorin in advanced neuroendocrine tumours.
Explore the source record for details and available documents.
Adult↗
Intracardiac metastases from neuroendocrine tumours.
We report three cases of intra-cardiac metastases from neuroendocrine tumours of the carcinoid type. One presented in a manner identical to a left atrial myxoma; in one patient a left atrial mass was noted during investigations for weight loss and a lung mass; and in the third, two right ventricular deposits were detected on echocardiography when a patient with a disseminated GHRH-secreting tumour was investigated for dyspnoea. Although to our knowledge this is only the third report of these lesions, we believe that this represents a form of carcinoid heart disease that is distinct from the valvular abnormalities seen in some patients with carcinoid syndrome. Neuroendocrine metastases should be considered in the differential diagnosis of intra-cardiac tumours.
Adult↗
Leptin levels do not change acutely with food administration in normal or obese subjects, but are negatively correlated with pituitary-adrenal activity.
BACKGROUND: Leptin is a peptide secreted by white adipose tissue which has been shown to have a major influence on body weight regulation, while animal studies have revealed widespread interconnections between leptin and other endocrine systems, especially with insulin. However, its acute regulation has been little studied in the human. We have therefore investigated the effect of a 1000 kcal meal and fasting on the levels of leptin, insulin and cortisol, in both normal and obese subjects. SUBJECTS AND DESIGN: We have studied the effect of food and fasting on circulating leptin levels in 20 subjects of normal body mass index (BMI range 18-25) and in a group of 12 moderately-severely obese subjects (BMI range 34-61). We also studied the effect of food and fasting in a patient both before and after the successful removal of a pancreatic insulinoma as a model of excess insulin secretion. RESULTS: Mean leptin levels were significantly higher in the obese than in the lean group (42.7 +/- 3.41 vs 5.35 +/- 1.55 micrograms/l, mean +/- SEM; P < 0.001), and showed a positive correlation with body mass index (r = +0.71; P < 0.001). Frequent (every 20 minutes) sampling for 3 hours after food did not show any acute changes in circulating leptin levels. On the fasting day we observed a small but significant fall in circulating leptin levels in the last 4 hours of a 20-hour fast in our subjects as a group (92 +/- 0.03% of basal, P = 0.03); however, in the lean subjects the fall was greater (86 +/- 0.04% of basal, P = 0.02) than in the obese, where it did not reach statistical significance (96 +/- 0.05% of basal). Pre-meal and peak insulin levels showed a positive correlation with circulating mean leptin levels (r = +0.65; P < 0.001 and r = +0.78; P < 0.001, respectively) in all subjects, while pre-meal and peak serum cortisol levels showed an inverse relation with leptin levels (r = -0.53; P = 0.002 and r = -0.41; P = 0.02, respectively); this effect was independent of BMI in the obese subjects. In the patient with the insulinoma the markedly elevated insulin and leptin levels measured before the operation returned to normal after removal of the tumour, in accord with reports of experimental animal data that long-term insulin excess per se is associated with increased circulating leptin concentrations. CONCLUSION: Leptin is a robust indicator of BMI and insulin levels, both basal and stimulated, but does not change acutely following food. Fasting causes a proportionately greater decline in leptin levels in lean subjects than in obese subjects. Circulating leptin is inversely correlated with the activity of the hypothalamo-pituitary-adrenal axis: whether this is a direct influence of leptin on hypothalamo-pituitary-adrenal activity, or whether both are indirect indicators of body fat stores, requires further investigation.
Adult↗
A comparison of the insulin tolerance/glucagon test with the short ACTH stimulation test in the assessment of the hypothalamo-pituitary-adrenal axis in the early post-operative period after hypophysectomy.
OBJECTIVE: The insulin tolerance test (ITT) is the established reference test for assessing the hypothalamo-pituitary-adrenal (HPA) axis. Various authorities, however, have suggested that the 250 microgram short ACTH stimulation test may be used to assess the HPA axis in place of the ITT in suspected hypopituitarism, although a number of other studies have suggested that the test may be unreliable in this setting. In this study, the ITT (or glucagon test) has been compared with the 250 microgram short ACTH stimulation test in patients with pituitary tumours pre-operatively and within 2 weeks of trans-sphenoidal hypophysectomy. DESIGN: An ITT, or a glucagon test when the ITT was contraindicated, and the 250 micrograms short ACTH stimulation test, were performed in all the patients before (an ITT in 18 and a glucagon test in three patients) and within 2 weeks after trans-sphenoidal hypophysectomy (an ITT in 16 and a glucagon test in five patients). PATIENTS: Twenty-one patients with pituitary disorders (15 with acromegaly, one with a prolactinoma and five with non-functioning tumours) were studied; four had a microadenoma, two a mesoadenoma and 15 a macroadenoma. MEASUREMENTS: Serum cortisol was measured by radioimmunoassay. A normal response was defined as a rise in serum cortisol to 580 nmol/l or above for all the tests. RESULTS: Before surgery, three of 18 patients (17%) had a discrepancy between the ITT and the 30 minute short ACTH stimulation test and one of three between the glucagon test and the 30 minute short ACTH stimulation test. Combined together, pre-operatively, four of 21 patients (19%) had discrepant results. In the early post-operative period, the discrepancy between ITT and the 30 minute short ACTH stimulation test was higher with four of 16 patients (25%) showing discordant results; one of the five patients tested had a discrepancy between the glucagon test and the 30 minute short ACTH stimulation test. On combining the tests, the post-operative discrepancy was five of 21 patients (24%). CONCLUSIONS: The 250 microgram short ACTH stimulation test produces discordant results from the ITT in a clinically significant proportion of affected patients when assessing the HPA axis, although the rate of discordance varies according to the criteria used for normality for both the tests. We suggest that the ITT should remain the preferred test for assessing ACTH secretory capacity compared with the standard 250 microgram short ACTH stimulation test, both in the preoperative and in the early post-trans-sphenoidal hypophysectomy period.
Adenoma↗
Metastatic parathyroid carcinoma in the MEN2A syndrome.
We report a patient with a metastatic parathyroid carcinoma and medullary carcinoma of the thyroid. This patient represents a variation of the multiple endocrine neoplasia syndrome (MEN) type 2A. There was no evidence of a phaeochromocytoma. The case illustrates the difficulties that may be encountered in localising the source of PTH secretion; the patient underwent four unsuccessful exploratory operations of the neck and mediastinum before further investigations revealed a single metastatic deposit of parathyroid carcinoma involving the first thoracic vertebra. PCR amplification and sequencing of the RET oncogene from the metastatic parathyroid carcinoma and genomic DNA revealed a heterozygous mutation (Cys634Tyr) in exon 11, as has previously been described to occur in MEN 2A. In addition, loss of tumour heterozygosity was demonstrated at loci from chromosomes 1, 2, 3p, 13q and 16p. This represents the first report of a parathyroid carcinoma in a MEN2A patient, in which the multiple allelic deletions are consistent with the generalised losses observed in aggressive tumours.
Carcinoma↗
When and how to transfer patients from paediatric to adult endocrinologists: experience from St Bartholomew's Hospital, London.
Explore the source record for details and available documents.
Adolescent↗
The potential for growth hormone in the management of heart failure.
Explore the source record for details and available documents.
Animals↗
Gonadotropin-releasing hormone immunoreactivity in the nasal epithelia of adults with Kallmann's syndrome and isolated hypogonadotropic hypogonadism and in the early midtrimester human fetus.
GnRH-secreting neurons are known to originate in the epithelium of the medial olfactory placode, whence they migrate along the axons of the terminal nerve via the forebrain and into the hypothalamus. Synaptic contact between the developing olfactory bulbs and fascicles of the vomeronasal, terminal, and olfactory nerves does not occur in Kallmann's syndrome. Consequently, there is migration arrest of GnRH cells and partial or complete failure of formation of the olfactory bulbs, resulting in severe olfactory deficit and hypogonadotropic hypogonadism. In the present study, using an immunofluorescent, double immunostaining technique and confocal laser scanning microscopy, we observed GnRH-immunoreactive neurons in the hypothalamus of a 14-week-old human fetus. However, migration of GnRH neurons was not complete, and indeed, such cells were seen to be migrating along terminal nerve fascicles beneath the cribriform plate in a 16-week-old fetus. The same immunofluorescent technique demonstrated the presence of GnRH cells in biopsies of nasal mucosa obtained from three adults with Kallmann's syndrome, one normosmic subject with hypogonadotropic hypogonadism, and a eugonadal male cadaver. These findings are consistent with two different interpretations: the nasal GnRH neurons may be vestigial, representing cells that failed to migrate during embryogenesis; alternatively, they may have been generated de novo later in life, a possibility consistent with the recognized plasticity of human postnatal olfactory neuroepithelium. They also reveal that subjects with the normosmic (i.e. non-Kallmann's) form of GnRH deficiency are able to synthesize immunologically recognizable GnRH, implying that failure of GnRH synthesis is not responsible for this type of hypogonadotropic hypogonadism.
Adult↗
Expression of glucocorticoid receptor gene isoforms in corticotropin-secreting tumors.
The molecular basis of Cushing's disease is not known. One of the most characteristic features of such tumors is their resistance to corticosteroid feedback at the pituitary level. We have hypothesized that abnormalities of the glucocorticoid receptor (GR) gene might play a role in the development of Cushing's disease via an increase in the relative production of the nonligand-binding splice variant of the GR, GR beta, known to exert dominant negative effects over the ligand-binding isoform, GR alpha. Alternatively, a change in overall GR expression, or mutations of some functional domains of the GR gene, might be involved in the pathogenesis of corticotroph tumors. We studied 22 tumors (17 pituitary ACTH-secreting tumors, 2 ectopic ACTH-producing tumors, 2 prolactinomas, and 1 nonfunctioning adenoma) and three normal pituitaries. RT-PCR was performed with primers specific to GR alpha and GR beta complementary DNA, followed by Southern blotting using an internal probe, and the ratio of the two bands quantitated by densitometry. We also assessed the overall expression of GR relative to the message of both the POMC gene and a housekeeping gene. Single-strand conformation polymorphism analysis of the DNA-binding domain and splice junction region of the gene was also performed. GR alpha messenger RNA was expressed at 37.3-fold +/- 5.7 (range, 32 to 46) excess, as compared with the GR beta subform. This pattern was observed both in the tumor samples and in the normal pituitaries used as controls. A majority of the ACTH-secreting tumors (16/19), including the ectopic secretors, showed variable but increased overall GR expression, whereas 3 tumors showed an expression approximately equivalent to the normal controls; however, no correlation was found between these two groups and the response to the high-dose dexamethasone test, nor was there any correlation with tumor histology. No mutations were found in any of the tumors by PCR-single-strand conformation polymorphism analysis. In conclusion, although both pituitary and ectopic ACTH-secreting tumors are at least partially glucocorticoid-resistant, no significant abnormalities in the relative expression of the two main GR subforms were observed in a series of such tumors. Additionally, mutations of regions critical to normal function of the receptor do not seem to be a frequent event in these tumors.
ACTH Syndrome, Ectopic↗
Clinical, radiological and pathological features of patients with Rathke's cleft cysts: tumors that may recur.
Rathke's cleft cysts are cystic sellar and suprasellar lesions, characteristically lined by a single layer of ciliated cuboidal or columnar epithelium. In contrast, craniopharyngiomass, which are also cystic sellar and suprasellar lesions, are characteristically lined by stratified squamous epithelium with keratinization on a layer of connective tissue. The usual management recommended for Rathke's cleft cysts is simple surgical drainage with partial excision of the cyst wall. Recurrences of these cysts reportedly have been very rare. This retrospective study presents the details of 12 patients (6 females; median age 30 yr, range 21-58 yr) with Rathke's cleft cyst, referred to our department over a 15-yr period (1981-1996), an unusual feature being the recurrence of 4 (33%) of these lesions. Clinical, endocrine, radiological, surgical (10 transsphenoidal; 2 transcranial), and pathological details were recorded. Nine out of 12 patients (75%) were symptomatic; visual symptoms were the commonest, and 8 had visual field defects. The median duration of symptoms was 12 months (range 3-24 months). Three patients (25%) had panhypopituitarism, 2 of whom also had diabetes insipidus (17%). The cysts varied in size from 6 mm to 50 mm, 1 being entirely suprasellar. There were no pathognomonic clinical or radiological features to differentiate them from other pituitary lesions, although the presence of diabetes insipidus in 2 patients suggested that the lesion was not a pituitary adenoma. A definite histological diagnosis was possible in 8 patients; in 4, the diagnosis was presumptive. The median duration of follow-up was 30 months (1-168 months). Four patients (33%) showed reexpansion at 3, 6, 48, and 48 months after initial surgery, 3 of whom were symptomatic and required repeat surgery. Two of these patients were given postoperative external beam pituitary radiotherapy. Apparent recurrence of Rathke's cleft cysts after initially successful surgery in our series was higher than suggested by previous reports, and thus, long-term follow-up with pituitary imaging and neuroophthalmological assessment is essential. There are no specific characteristics of the cyst that predict recurrence. Ideal management of these cysts is unclear, but aspiration, followed by extensive excision of the cyst wall when possible, seems to be the best initial option. For recurrent symptomatic tumors, surgical resection is the treatment of choice. Considering the high recurrence rate with residual structural and functional dysfunction, the role of radiotherapy in preventing recurrence of these cysts needs careful evaluation with a larger study with a longer follow-up period.
Adult↗
Normal growth hormone secretion in growth hormone insufficient children retested after completion of linear growth.
OBJECTIVE: The recognition of the syndrome of adult GH deficiency suggests that young GH deficient adults, deprived of GH replacement at completion of linear growth, may suffer effects of GH deficiency. We assessed GH reserve in young adults previously diagnosed as having idiopathic GH insufficiency, who were treated with hGH replacement (14 IU/m2/week) in childhood. DESIGN: Eight patients (7 males, 1 female) diagnosed as having GH insufficiency by insulin tolerance test (ITT) in childhood (ages 8.5-15.6 years) were retested by ITT at completion of linear growth (ages 15.1-19.6 years), 3 months after discontinuation of hGH therapy. MEASUREMENTS: GH reserve was measured during ITT at diagnosis and at retesting. Height velocity (HV) and HV SDS were calculated before and during GH therapy. RESULTS: At diagnosis, the mean peak GH response to ITT was 10.5 +/- 2.0 mU/l (range 7.7-13.6). At retesting, mean GH was 52.4 +/- 33.2 mU/l (range 10.4-100), 7/8 subjects having peak GH levels greater than 15 mU/l. During hGH therapy mean HV increased from 4.0 +/- 1.5 cm/year at diagnosis to 7.3 +/- 1.9 cm/year during the 1st year (P = 0.004) and 6.9 +/- 2.3 cm/year during the 2nd year (P = 0.02). Mean HVSDS increased from -1.6 +/- 2.1 at diagnosis to 3.1 +/- 2.9 during the 1st year (P = 0.004) and 2.2 +/- 4.2 during the 2nd year (P = 0.05, NS) of treatment. CONCLUSIONS: Seven out of 8 children diagnosed as having idiopathic GH insufficiency had normal GH secretion at completion of linear growth. Children with GH insufficiency cannot be assumed to become GH deficient adults and should not continue on GH therapy into adult life without reinvestigation. All who were GH insufficient children should be retested at completion of linear growth to identify those who are truly GH insufficient adults and may benefit from replacement therapy.
Adolescent↗
Oral prednisolone supplement abolishes the acute adverse effects following initiation of depot bromocriptine therapy.
OBJECTIVE: Although an effective treatment for hyper-prolactinaemia, initiation of bromocriptine therapy may be associated with significant acute side-effects in some patients, particularly nausea, vomiting and postural hypotension. These may be minimized by initial treatment with i.m. depot bromocriptine (Parlodel-LAR, Sandoz, Basel, Switzerland), but adverse effects following the first injection may still be a significant problem. Following the observation that cortisol deficient patients were subject to an increased incidence of severe side-effects on initiation of bromocriptine therapy, we have evaluated whether concurrent administration of oral prednisolone to patients without cortisol deficiency might reduce adverse effects. DESIGN: Double-blind placebo-controlled trial with prednisolone (20 mg) prior to, and 16 hours after, depot injection of i.m. bromocriptine (50 or 100 mg). PATIENTS: Twenty-one consecutive patients with hyperprolactinaemia (serum prolactin > 1000 mU/l on 3 separate occasions) who were due to start depot bromocriptine and who had a normal cortisol response to insulin-induced hypoglycaemia. MEASUREMENTS: Symptoms at 0, 16 and 40 hours after injection were assessed using visual linear analogue scales and both inter and intra-group scores were compared by non-parametric tests. RESULTS: Depot bromocriptine was associated with the significant occurrence of light-headedness and lethargy in the placebo-administered group by 16 hours, and also with nausea and nasal congestion by 40 hours. These symptoms did not occur in the prednisolone-administered group. CONCLUSIONS: Concurrent oral administration of prednisolone significantly reduces the incidence of acute adverse effects following depot bromocriptine. Two 20 mg doses of prednisolone given at 12-hour intervals may be used to avoid dopamine-agonist-induced adverse effects at the initiation of treatment with depot bromocriptine, and may also be of value in the treatment of side-effects associated with other dopamine agonist drugs.
Administration, Oral↗
Outcome of transsphenoidal surgery for acromegaly using strict criteria for surgical cure.
OBJECTIVE: Previous studies of surgical treatment for acromegaly have used varied criteria for 'cure', but elevated GH levels are considered to be associated with continuing disease activity. We wished to analyse the results of transsphenoidal pituitary surgery for acromegaly and assess the longer-term outcome for patients not offered further treatment when post-operative levels of GH < 5 mU/l were achieved. DESIGN: We studied a retrospective group of patients who underwent transsphenoidal surgery for acromegaly at St Bartholomew's Hospital between 1985 and 1993. PATIENTS: One hundred consecutive patients (53 male, mean age 46 years, range 18-68 years) undergoing transsphenoidal surgery for acromegaly were assessed. The patients were followed for a mean of 3.8 years (range 0.5-8 years) after operation. MEASUREMENTS: GH levels are represented as a mean value from a four-point day curve taken at 0830, 1300, 1700 and 1900 h. ACTH reserve was assessed basally and, if this was normal, with the insulin tolerance or glucagon tests. TSH, T4, PRL, LH, FSH, testosterone or oestradiol and plasma and urine osmolality were also measured. RESULTS: Post-operatively, 42% of patients achieved a mean GH level of < 5 mU/l. The success of surgery was related to the preoperative GH level; 65% of the patients with preoperative GH levels < 20 mU/l but only 18% of the patients with GH levels > 100 mU/l achieved post-operative GH values < 5 mU/l. In addition, tumour size influenced the outcome of surgery with 61% of patients with a microadenoma but only 23% of patients with a macroadenoma achieving post-operative GH levels of < 5 mU/l. Of the 42 patients considered in remission post-operatively (mean GH < 5 mU/l), 32 were available for long-term follow-up and were not offered any further treatment: only one of these has shown evidence of mild biochemical recurrence after a mean follow-up of 3.8 years (range 0.5-8). There were no peri-operative deaths. Two patients required surgical repair for CSF leaks and there were eight documented cases of meningitis. Permanent diabetes insipidus was noted in eight patients post-operatively. New anterior pituitary deficiency occurred in 21% of patients following surgery; 73% had unaltered pituitary function and in 6% recovery of partial hypopituitarism was noted. CONCLUSIONS: The stated outcome of surgery depends on the criteria adopted. Safe GH levels (mean levels < 5 mU/l) can be achieved in 42% of an unselected series of patients with acromegaly and if the tumour is a microadenoma this figure rises to 61%. Based on the current evidence it is safe not to offer further treatment to those patients in whom post-operative GH < 5 mU/l are achieved.
Acromegaly↗
Differential stimulation of cortisol and dehydroepiandrosterone levels by food in obese and normal subjects: relation to body fat distribution.
BACKGROUND: It has been previously shown that food intake elevates circulating ACTH and cortisol levels, but no report has been published regarding the changes in circulating dehydroepiandrosterone (DHEA). DHEA was originally described as a weak androgen, but more recently it has been associated with a wide range of metabolic functions. In addition, previous studies have described a hyper-responsive hypothalamo-pituitary-adrenal axis in obese subjects in response to various stimuli, but the specific response to food has not been studied. SUBJECTS AND DESIGN: We studied the effect of food on the hypothalamo-pituitary-adrenal axis in 20 subjects of normal body mass index (BMI range 18-25) and also in a group of 12 obese subjects (BMI range 34-61). Levels of glucose, insulin, ACTH, cortisol and dehydroepiandrosterone were measured every 20 minutes. RESULTS: A small rise in DHEA accompanies the rise in circulating ACTH and cortisol in response to food in both lean and obese subjects, but DHEA rose independently of cortisol and ACTH on the fasting day. In the obese subjects, food induced a significantly greater change in serum cortisol (peak cortisol rise (mean +/- SEM); normal-weight group, 169 +/- 14%; obese group, 294 +/- 23%) and in the cortisol/DHEA ratio (area under the curve; normal-weight group, 202 +/- 15%; obese group, 292 +/- 29%) than in the normal-weight subjects. This difference was particularly notable in those with central-type obesity (waist/hip ratio > 0.80). A group of the normal, jean female subjects showed no cortisol rise after food intake. CONCLUSION: Our results suggest that DHEA may vary independently of circulating cortisol, and that the cortisol response to food is enhanced in obese subjects, particularly in those with central obesity. We speculate that there may be a caused connection between the cortisol response to food in normal subjects, and the subsequent distribution of fat if such subjects overeat sufficiently to become obese.
Adipose Tissue↗
Clinical studies of multiple endocrine neoplasia type 1 (MEN1)
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined occurrence of parathyroid, pancreatic islet and anterior pituitary tumours. To facilitate a screening programme for MEN1, we investigated 709 people (364 males and 345 females, age range 1-84 years) from 62 MEN1 families, and 36 non-familial MEN1 patients. Of those investigated, 220 (95 males and 125 females, age range 8-79 years) suffered from MEN1. Parathyroid, pancreatic and pituitary tumours occurred in 95%, 41% and 30% of the patients, respectively. Parathyroid tumours were the first manifestation of MEN1 in 87% of patients, and amongst the pituitary and pancreatic tumours, somatotrophinomas and gastrinomas were more common in patients above the age of 40 years, whilst insulinomas occurred more frequently in patients below the age of 40 years. Biochemical screening indicated that the penetrance of MEN1 by the ages of 20, 35 and 50 years was 43%, 85% and 94%, respectively, and that the development of MEN1 was confined to first-degree relatives in 91% of patients and to second-degree relatives in 9% of patients. These findings have helped to define a proposed screening programme for MEN1.
Adolescent↗
Growth hormone treatment in hypopituitary GH deficient adults reduces circulating cortisol levels during hydrocortisone replacement therapy.
OBJECTIVES: Patients with GH deficiency frequently have multiple hormone deficiencies and require hydrocortisone replacement. We have investigated whether GH treatment alters circulating cortisol levels in hypopituitary patients receiving stable replacement therapy. DESIGN: Subjects were studied during 6 or 12 months of s.c. GH at a dose of 0.25 IU/kg/week (0.125 IU/kg/week for the first 4 weeks), and after a wash-out period of at least 2 months off GH (range 2-5 months). PATIENTS: Fourteen hypopituitary patients (2F:12M) receiving stable hydrocortisone replacement and thyroxine, gonadal steroids and bromocriptine therapy as required. MEASUREMENTS: Serum cortisol values were measured throughout the day over 10.5 hours. Thyroid hormones and cortisol binding globulin (CBG) were measured in the baseline sample. Comparisons of the serum cortisol peak after receiving the first dose of hydrocortisone, the time when the serum cortisol peak was obtained, the area under the curve (AUC) for the cortisol values and the levels of unbound cortisol on and off GH therapy were made. The results are expressed as mean +/- SEM. Comparisons were carried out within individuals, using the Wilcoxon signed rank test. A P-value less than 0.05 was considered statistically significant. RESULTS: During GH therapy, there was a significant reduction in the mean cortisol peak (662.2 +/- 61.1 vs 848.0 +/- 58.6 nmol/l; P = 0.001), and in the AUC for cortisol (185.3 +/- 18.3 vs 230 +/- 17.9 nmol/l/10.5h; P = 0.03), but there was no significant change in the time of the cortisol peak (55.7 +/- 7.6 vs 57.8 +/- 4.9 minutes; P = NS). During GH therapy there was a significant reduction in CBG levels (33.64 +/- 1.16 vs 40.86 +/- 1.34 mg/l; P = 0.001); however, no changes were found in the levels of calculated unbound cortisol on and off GH (2.87 +/- 0.38 vs 2.90 +/- 0.30 nmol/l; P = NS). During GH therapy, there was a significant increase in serum triiodothyronine (T3) (1.88 +/- 0.15 vs 1.44 +/- 0.11 nmol/l; P = 0.01), and a significant decrease in thyroxine (T4) levels (74.9 +/- 11.1 vs 97.6 +/- 10.9 nmol/l; P = 0.02) but levels remained within the normal range. No change was observed in serum TSH levels (0.29 +/- 0.13 vs 0.83 +/- 0.71 mU/l; P = NS). CONCLUSIONS: These results suggest that GH therapy in GH deficient adults produces an alteration in the measured serum cortisol profile, with a reduction in concentration of total cortisol in blood after orally administered hydrocortisone. These changes in circulating cortisol probably depend primarily on the fall in CBG levels, as no changes were found in the levels of calculated unbound cortisol on and off GH. Our data show that when measuring circulating cortisol levels, the results should be interpreted with caution in GH deficient patients on GH replacement, and different criteria may have to be applied to the circulating cortisol profile of these patients. The results highlight the importance of ensuring adequate corticosteroid replacement in patients starting GH therapy.
Adult↗
The accuracy of parathyroid gland localization in primary hyperparathyroidism using sestamibi radionuclide imaging.
Primary hyperparathyroidism is a common condition due to either a parathyroid adenoma or, less commonly, parathyroid hyperplasia, whose treatment is essentially surgical. We have, therefore, assessed the accuracy of Tc-99m pertechnetate/Tc-99m sestamibi (methoxy-isobutyl isonitrile) imaging in the localization of adenomas and hyperplastic parathyroids. The clinical records of all patients who had Tc-99m pertechnetate/Tc-99m sestamibi imaging and parathyroid surgery at this hospital were reviewed. The technique used involves standard subtraction methodology with the addition of a novel change detection algorithm to optimize localization. Of 46 patients scanned in 48 patient episodes, 36 patients had adenomas; 28 (78%) were accurately localized to the correct quadrant, and 4 were correctly lateralized. Two patients with parathyroid carcinomas had their metastases correctly localized. Thus, in 34 of 38 (89.5%) of the scans, adenomas or carcinomas were able to be anatomically localized. Six patients presented with hyperplasia; 5 were diagnosed by sestamibi scans, and 3 of these accurately localized all hyperplastic glands. Four additional patients had known hyperplasia, of which 2 were rendered normocalcemic after removal of their sestamibi-positive glands; the other 2 had small second glands detected only at surgery. In patients with unknown pathology, imaging suggested that 6 patients had hyperplasia; this was correct in 5 cases (83%). Nine of the 12 scans in patients who had had previous parathyroid surgery accurately localized the tumors, 7 in the neck and 2 outside. We suggest that sestamibi imaging can help to distinguish hyperplasia from adenomatous disease; when imaging is required, we recommend it as the imaging modality of choice in all patients with primary hyperparathyroidism, especially in reoperated patients.
Adenoma↗