A cross-sectional study of the prevalence of cardiac valvular abnormalities in hyperprolactinemic patients treated with ergot-derived dopamine agonists.

CONTEXT: Concern exists in the literature that the long-term use of ergot-derived dopamine agonist drugs for the treatment of hyperprolactinemia may be associated with clinically significant valvular heart disease. OBJECTIVE: The aim of the study was to determine the prevalence of valvular heart abnormalities in patients taking dopamine agonists as treatment for lactotrope pituitary tumors and to explore any associations with the cumulative dose of drug used. DESIGN: A cross-sectional echocardiographic study was performed in a large group of patients who were receiving dopamine agonist therapy for hyperprolactinemia. Studies were performed in accordance with the British Society of Echocardiography minimum dataset for a standard adult transthoracic echocardiogram. Poisson regression was used to calculate relative risks according to quartiles of dopamine agonist cumulative dose using the lowest cumulative dose quartile as the reference group. SETTING: Twenty-eight centers of secondary/tertiary endocrine care across the United Kingdom participated in the study. RESULTS: Data from 747 patients (251 males; median age, 42 y; interquartile range [IQR], 34-52 y) were collected. A total of 601 patients had taken cabergoline alone; 36 had been treated with bromocriptine alone; and 110 had received both drugs at some stage. The median cumulative dose for cabergoline was 152 mg (IQR, 50-348 mg), and for bromocriptine it was 7815 mg (IQR, 1764-20 477 mg). A total of 28 cases of moderate valvular stenosis or regurgitation were observed in 24 (3.2%) patients. No associations were observed between cumulative doses of dopamine agonist used and the age-corrected prevalence of any valvular abnormality. CONCLUSION: This large UK cross-sectional study does not support a clinically concerning association between the use of dopamine agonists for the treatment of hyperprolactinemia and cardiac valvulopathy.

Cluster headache secondary to macroprolactinoma with ipsilateral cavernous sinus invasion.

We present a 25 year-old man with episodic cluster headache that was refractory to all standard pharmacological prophylactic and abortive treatments. Because of the lack of response, an MRI brain was performed which showed a large pituitary tumour with ipsilateral cavernous sinus invasion. The serum prolactin was significantly elevated at 54,700 miU/L (50-400) confirming a macro-prolactinoma. Within a few days of cabergoline therapy the headache resolved. He continues to be headache free several years after starting the dopamine agonist. This case highlights the importance of imaging the pituitary fossa in patients with refractory cluster headache, It also raises the potential anatomical importance of the cavernous sinus in pituitary-associated headache.

Home administration of lanreotide Autogel by patients with acromegaly, or their partners, is safe and effective.

OBJECTIVE: The introduction of ready-to-use lanreotide Autogel has presented the possibility of patients receiving their acromegaly treatment at home. The objective of this study was to assess the ability of patients (or their partners) to administer repeat, unsupervised, injections of lanreotide Autogel without compromising efficacy or safety. DESIGN: Multicentre (10 UK regional endocrine centres), open-label, nonrandomised, controlled study. Patients elected either to receive/administer unsupervised home injections after injection technique training (Test group) or continued to receive injections from a healthcare professional (Control group). Patients received monthly injections of lanreotide Autogel at their established dose. Effects were monitored for up to 40 weeks. PATIENTS: Thirty patients (15 per treatment group) with acromegaly treated with a stable dose of lanreotide Autogel (60, 90 or 120 mg) for > or = 4 months before screening. Measurements The main outcome measure was the proportion of patients/partners who successfully administered injections throughout the study. RESULTS: All Test group patients/partners qualified to administer injections. Fourteen of 15 patients fulfilled all criteria for successful administration of unsupervised injections (95% confidence interval, 70%-99%). Fourteen of 15 Test and 14/15 Control patients maintained growth hormone and IGF-1 control. Local injection tolerability was good for both treatment groups, and safety profiles were similar. All Test group patients continued with unsupervised injections after the study. CONCLUSIONS: Patients with acromegaly or their partners were able to administer lanreotide Autogel injections with no detrimental effect on efficacy and safety; therefore, unsupervised home injections are a viable alternative to healthcare professional injections for suitably motivated patients.

Pituitary apoplexy: retrospective review of 30 patients--is surgical intervention always necessary?

The objective of this article is to review clinical outcomes in patients presenting with pituitary apoplexy and compare the results of conservative and surgical management. It took the form of a retrospective review of 30 patients (23M, 7F; age range: 17-86 years) with pituitary apoplexy diagnosed between 1988 and 2004. Presenting features included headache in 27 patients, 'collapse' in three and vomiting in 14. Complete blindness occurred in four patients, monocular blindness in two, decreased visual acuity in 12, visual field loss in 10 and ophthalmoplegia in 15. Only five had no initial visual deficit. CT was the initial mode of imaging in 22 patients: three such scans were initially reported as 'normal' and a further 10 as pituitary tumour only, with no haemorrhage. Ten patients proceeded to early pituitary surgery and 20 were managed conservatively. There was one death 24 days after admission in a patient with multiple co-morbidities. Of the six patients with blindness, three (two conservatively treated) regained partial vision. Of the remaining 19 patients with visual deficits, 10 (two surgically treated) recovered fully and eight (four surgically treated) partly so. At latest follow-up the following pituitary hormone deficiencies were identified: ACTH 19; TSH 20; testosterone 18; ADH (diabetes insipidus) eight. Later recurrence of a pituitary adenoma was observed in seven cases (including six of the 10 surgically treated patients). There was no evidence that those patients managed surgically had a better outcome. Early neurosurgical intervention may not be required in most patients presenting with pituitary apoplexy.

Pituitary incidentalomas.

The optimal strategy for hormonal screening of a patient with any incidentally discovered pituitary mass is unknown. The authors' review of the endocrinologic literature supports the view that such patients are at slightly increased risk for morbidity and mortality. This risk implies a benefit of early diagnosis for at least for some of the disorders, suggesting the importance of case finding. Nevertheless, the data in Table 1 illustrate that clinically diagnosed hormone-secreting pituitary tumors are far less common than incidentalomas. Clinically, one cannot accurately determine the approximately 0.5% of patients with incidentaloma who are at increased risk among the vast majority who are not. Given the limitations of diagnostic tests, effective hormonal screening requires a sufficiently high pretest probability to limit the number of false-positive results. This condition is met to varying degrees in the patient with a small incidentally discovered pituitary mass but no signs or symptoms of hormone excess. Even the more common lesions, such as prolactinoma, are relatively rare. [table: see text] Subjecting patients to unnecessary testing and treatment is associated with risk. In addition to its initial cost, testing may result in further expense and harm as false-positive results are pursued, producing the "cascade effect" described by Mold and Stein as a "chain of events (which) tends to proceed with increasing momentum, so that the further it progresses the more difficult it is to stop." The extensive evaluations performed for some patients with incidentally discovered masses may reflect the unwillingness of many physicians to accept uncertainty, even in the case of an extremely unlikely diagnosis. This unwillingness may be driven, in part, by fear of potential malpractice liability, the failure to appreciate the influence of prevalence data on the interpretation of diagnostic testing, or other factors. The major justification for further evaluation of these patients is not so much to avoid morbidity and mortality for the rare patient who truly is at increased risk but to reassure patients in whom further testing is negative and the physician. Physicians must take care not to create inappropriate anxiety in patients by overemphasizing the importance of an incidental finding unless it is associated with a realistic clinical risk. The authors' recommendations are based on currently available information to minimize the untoward effects of the cascade. As evidence accumulates, these recommendations may need to be revised. The benefit of the diagnosis of an adrenal or pituitary disorder must be considered in the context of the patient's overall condition. Additional studies are needed to analyze the clinical utility of hormonal screening for these common radiologic findings. Data from these studies can be used to identify critical gaps in knowledge and to adopt the epidemiologic methods of evaluation of evidence that have been applied to preventive measures. One must be careful to recognize lead-time bias, in which survival can appear to be lengthened when screening simply advances the time of diagnosis, lengthening the period of time between diagnosis and death without any true prolongation of life; and length bias, which refers to the tendency of screening to detect a disproportionate number of cases of slowly progressive disease and to miss aggressive cases that, by virtue of rapid progression, are present in the population only briefly. Physicians must avoid the pitfalls of overestimation of disease prevalence and of the benefits of therapy resulting from advances in diagnostic imaging. Clinical judgment based on the best available evidence should be complemented and not replaced by laboratory data.

Management of pituitary incidentalomas. A survey of British and American endocrinologists.

The results of a survey of endocrinologists concerning their approaches to the evaluation of a patient with an incidentally discovered pituitary mass are presented in this article. The practices of British and American endocrinologists are compared. The wide variation in diagnostic approaches to the practice of ordering tests in the United Kingdom and the United States highlights the need for research and debate regarding the most appropriate management of patients with such findings.

A defect in the regional deposition of adipose tissue (partial lipodystrophy) is encoded by a gene at chromosome 1q.

Partial lipodystrophy (PLD), also known as "Dunnigan-Kobberling syndrome," is transmitted as a highly penetrant autosomal dominant disorder that is characterized by a dramatic absence of adipose tissue in the limbs and trunk, more evident in females than in males. In contrast, fat is retained on the face, in retro-orbital space, and at periserous sites. Associated metabolic abnormalities, including insulin resistance, hyperinsulinemia, and dyslipidemia, are referred to as "metabolic syndrome X" (Reaven 1988). Despite the intense interest in the genetic determinants underlying fat deposition, the genes involved in the lipodystrophic syndromes have not been identified. We ascertained two multigeneration families, with a combined total of 18 individuals with PLD, and performed a genomewide search. We obtained conclusive evidence for linkage of the PLD locus to microsatellite markers on chromosome 1q21 (D1S498, maximum LOD score 6.89 at recombination fraction .00), with no evidence of heterogeneity. Haplotype and multipoint analysis support the location of the PLD locus within a 21.2-cM chromosomal region that is flanked by the markers D1S2881 and D1S484. These data represent an important step in the effort to isolate and characterize the PLD gene. The identification of the gene will have important implications for the understanding of both developmental and metabolic aspects of the adipocyte and may prove useful as a single-gene model for the common metabolic disorder known as "syndrome X."

Correcting impotence in the male dialysis patient: experience with testosterone replacement and vacuum tumescence therapy.

Sexual dysfunction remains a common and often distressing problem in the male dialysis population. Traditionally its management has consisted of correction of anemia, optimization of dialysis, removal of implicated medication, and finally depot injections of a testosterone ester. At a dedicated renal impotence clinic, we studied the effectiveness of testosterone replacement in men with biochemically proven hypogonadism and then vacuum tumescence therapy in those with continued erectile dysfunction. Depot testosterone was given to 27 patients (aged 52.4+/-2.5 years; duration of dialysis, 2.00+/-0.40 years; and duration of sexual dysfunction, 2.92+/-0.49 years): sexual function was fully restored in only three (11.1%), and two gradually lost the response over 18 months. Nineteen patients (70.3%) had partial responses, varying from an increased sense of well-being alone to restored sexual function apart from an impairment of the duration of penile erection. Five patients (18.5%) had no response, and testosterone was contraindicated in another four. Four of the treated patients (14.8%) reported fluid retention. Vacuum tumescence devices were then offered to 32 patients who remained impotent but declined by six. Twenty-six patients (aged 49.6+/-2.2 years; duration of dialysis, 2.50+/-0.58 years; and duration of sexual dysfunction, 3.26+/-0.56 years) used the devices, with 19 (73.1%) having full correction of their erectile dysfunction; six also continued with depot testosterone to maintain their libido. Penile discomfort was described by five patients (19.2%) whose potency was not restored. A further five predialysis patients have used the devices, and all had correction of their erectile dysfunction. The correction of biochemical hypogonadism in the male dialysis population with testosterone rarely restores sexual function to normal, whereas vacuum tumescence therapy corrects penile erection dysfunction in most patients.

Cabergoline treatment of acromegaly: a preliminary dose finding study.

OBJECTIVES: Studies of the dopamine agonist cabergoline in the treatment of hyperprolactinaemia have shown it to be a potent, long-acting and well-tolerated. The older dopamine agonist, bromocriptine, has traditionally had a place in the medical management of acromegaly, but poor patient tolerance of the high doses required, the need for multiple daily administration and incomplete biochemical responses have limited its role. We therefore sought to investigate the effect of cabergoline on growth hormone (GH) secretion in acromegaly and to define the most appropriate dose for suppression of GH DESIGN AND MEASUREMENTS: Patients with active acromegaly (defined as most recent random GH > 5 mU/l) were identified from the departmental clinical information system. After informed consent was obtained, basal GH levels were estimated during a 5 point day curve at least 2 months after withdrawal of any existing medical therapy for acromegaly. The cabergoline dose was escalated on a monthly basis for 4 months with a repeat 5 point GH day curve at the highest dose, and 0900 and 0930 GH estimations at the intermediate dose increment stages. Serum IGF-1 and prolactin were estimated on each occasion. Biochemical remission was defined as serum GH < 5 mU/l. PATIENTS: Eleven acromegalics were investigated. Previous treatment included surgery (7), radiotherapy (5) and bromocriptine (5). Three patients had not received any previous treatment. All had random GH persistently > 5 mU/l prior to the study. RESULTS: Ten patients completed the study. Of these, 7 showed a fall in the GH to < or = 33% and IGF-1 to < or = 67% of the basal value but only 2 achieved biochemical remission. All subjects showed maximum GH response at a dose of 0.5 mg daily of cabergoline. Four patients were unable to tolerate the maximum dose of 1 mg daily (nausea in one and nonspecific symptoms in three). The patient excluded from the analysis discontinued cabergoline and underwent surgery after 1 month because of worsening visual field defects. CONCLUSIONS: Cabergoline may be a useful adjunct to the currently available treatment for acromegaly, but rarely achieves the goal of mean GH < 5 mU/l. The maximum suppression of GH is achieved within the dose range 1 mg twice weekly to 0.5 mg daily.

Erythropoietin and sexual dysfunction.

BACKGROUND: Erythropoietin (rHuEpo) therapy has been shown to improve sexual function in the male dialysis population, with several studies suggesting a direct effect upon endocrine function, as well as correction of anaemia. Nevertheless many male dialysis patients receiving rHuEpo continue to complain of sexual dysfunction. METHODS: At a dedicated renal impotence clinic, 65 male dialysis patients were screened for endocrine disturbances. Baseline serum sex hormones were compared between those receiving and not receiving rHuEpo, using either the two-sample t test or the Mann-Whitney U test, after assessing for normality. Results from four patients were excluded on account of either medications (antiemetic phenothiazines), hepatic dysfunction, or carcinomatosis. RESULTS: Twenty-five patients (41.0%) were receiving rHuEpo, the recipients and non-recipients being well matched for haemoglobin (10.19 +/- 0.29 vs 10.55 +/- 0.25 g/dl, n.s.), age (51.1 +/- 1.9 vs 53.6 +/- 2.1 years, n.s.) and duration of sexual dysfunction (median, 3.0 vs 3.0 years, n.s.). The rHuEpo recipients had a higher median creatinine (1090 vs 972 micromol/l, P < 0.02), but similar nutritional status to the non-recipients (albumin 41.0 vs 39.0 g/l, n.s.). The total duration of rHuEpo therapy was 0.85 +/- 0.14 years. Prolactin levels were similar in both the rHuEpo recipients and non-recipients (440 vs 541 mu/l, n.s.), as were LH (11.0 vs 10.5 iu/l, n.s.) and FSH (8.0 vs 6.5 iu/l, n.s.). However, there were significant elevations of testosterone (19.8 +/- 1.3 vs 16.1 +/- 1.1 nmol/l, P < 0.05) and sex hormone binding globulin (SHBG) (40.5 vs 26.0 nmol/l, P < 0.01), with a trend toward elevated oestradiol (304 vs 248 pmol/l, P = 0.095) in the rHuEpo-treated group. Forty-eight subjects (78.7%) received peritoneal dialysis (PD), with the 19 rHuEpo recipients (39.6%) demonstrating increased serum testosterone (21.0 +/- 1.5 vs 16.6 +/- 1.3 nmol/l, P < 0.05), SHBG (40.5 vs 26.5 nmol/l, P < 0.01), LH (15.0 vs 10.0 iu/l, P < 0.01) and FSH (12.0 vs 5.3 iu/l, P < 0.05). These differences were not demonstrated in the 13 haemodialysis (HD) subjects. CONCLUSIONS: Male dialysis patients complaining of sexual dysfunction after correction of anaemia with rHuEpo are characterized by higher levels of serum testosterone and SHBG, but not suppression of hyperprolactinaemia or hyperoestrogenism. Male PD subjects receiving rHuEpo also demonstrated increased LH and FSH.

An assessment of optimal hydrocortisone replacement therapy.

OBJECTIVE: To assess the management of hydrocortisone replacement therapy in one institution, and derive recommendations for optimum starting and maintenance replacement therapy with hydrocortisone. DESIGN: Retrospective survey of clinical management using a clinical information system and the patient case notes. PATIENTS: Using the department's clinical information system, 210 patients were identified who had been treated with hydrocortisone. Case notes were reviewed and 130 patients were identified whose records contained the results of at least one valid hydrocortisone day curve. Data on 174 day curves performed on these patients (65 on twice daily and 109 on thrice daily hydrocortisone regimes) formed the basis of this analysis. METHODS: Hydrocortisone day curves had been performed as part of routine clinical management: patients collected a 24 h urine for free cortisol on the day prior to the test and took their morning hydrocortisone at the normal time, at home, on wakening. During a day-case attendance serum cortisol was then measured at 0900 h, 1230 h (prior to any lunchtime dose) and 1730 h (prior to the evening dose). 'Optimal replacement' was arbitrarily defined as that dose which achieved a UFC and 09:00 h cortisol within the reference range for the normal population (to avoid over-replacement) combined with 1230 h and 1730 h cortisol above 50 nmol/l, and ideally above 100 nmol/l (to avoid under-replacement). Raw data from all hydrocortisone day curves was analysed in an Excel spreadsheet to determine the effect of different dose regimens on the percentage of patients achieving each and all of these 4 criteria, and on an overall 'quality score' (comprising 1 point for each of the 4 criteria attained). RESULTS: Patients on twice daily hydrocortisone regimes achieved optimal replacement in 15% of cases compared to 60% on thrice daily regimes (P < 0.001 by chi 2); mean overall 'quality scores' for these regimens were 2.72 and 3.49 respectively (P < 0.001 by t-test). Of individual dose regimens with sufficient cases for valid comparison, a dose of 10 mg/5 mg/5 mg (rising/lunch/evening) achieved optimal replacement in 66% and mean 'quality score' of 3.62 (n = 53), compared to 50% and 3.32 for 10 mg/ 10 mg/5 mg (n = 28) and 10% and 2.48 for 20 mg/-/10 mg (n = 29). CONCLUSIONS: The use of arbitrary, but logical, criteria to assess the quality of hydrocortisone replacement regimens indicates that optimal replacement is achieved with thrice daily hydrocortisone regimens, and that the traditional twice daily regime results in a 0900 h cortisol above normal in one-third, and late afternoon cortisol below 50 nmol/l in one-half of patients thus treated. An appropriate starting dose of hydrocortisone of 10 mg/5 mg/5 mg (rising/lunch/evening) is suggested, with subsequent individual adjustment based on simple hydrocortisone day curves.

Dunnigan-Kobberling syndrome: an autosomal dominant form of partial lipodystrophy.

Dunnigan-Kobberling syndrome is a form of partial lipodystrophy characterized by sparing of the face. Despite descriptions of six families since 1974, details of total body adipose tissue distribution and studies of carbohydrate and fat metabolism are lacking. The mode of inheritance also remains unclear, with most authors favouring an X-linked dominant transmission lethal in the hemizygous male. We examined 23 members of a family, of whom at least eight had partial lipodystrophy. Auxological evaluation and cross-sectional imaging showed absence of subcutaneous fat, presence of adipose tissue inside the body cavities, and skeletal muscle hypertrophy. Biochemical evaluation identified insulin resistance but revealed inadequate suppression of non-esterified fatty acids. In this family, male-to-male transmission supports an autosomal dominant mode of inheritance for Dunnigan-Kobberling syndrome.

A survey of the current methods used in the UK to assess pituitary function.

A national survey of the current methods used by specialists to evaluate pituitary function in the UK was performed by postal questionnaire. Seventy-three respondents, of whom 89% were consultants and 80% clinical endocrinologists, returned the questionnaire. Fifty per cent routinely used the insulin stress test (IST) to evaluate the hypothalamo-pituitary-adrenal (HPA) axis, while 50% routinely used tetracosactrin stimulation, there being little overlap between the two groups. This represents a significant change in clinical practice since the last survey in 1988. In those who used ACTH stimulation there was almost an equal split into those who administered the tetracosactrin intramuscularly (45%) or intravenously (47%). Furthermore, either the peak or 60 min cortisol value was used by 71% when interpreting the result of the test, despite the fact that in previous studies only the 30 min cortisol value has been shown to correlate with the IST result. The IST remains the most frequently used method to assess growth hormone reserve in adult subjects. The thyrotrophin-releasing-hormone and gonadotrophin-releasing-hormone tests are still used routinely by approximately a quarter of clinicians. These results provide data that could be used to develop guide-lines for the use of tests to investigate pituitary function.

The use of the short tetracosactrin test for the investigation of suspected pituitary hypofunction.

The short Synacthen (tetracosactrin) test (SST) is an established method of assessing adrenocortical reserve, and is increasingly replacing the insulin tolerance test (ITT) for the assessment of the hypothalamic-pituitary-adrenal (HPA) axis. However, there is no consensus on how the test is performed, and various time points and routes of administration are used. The present study was done, first, to determine whether there was any difference in cortisol responses when Synacthen was administered intramuscularly compared with intravenously and, secondly, to compare cortisol responses at 30 and 60 min. We found no significant difference between the two routes of administration. However, cortisol responses at 60 min were significantly higher than at 30 min (P < 0.05). Previous validations for the use of the SST in place of the ITT have used cortisol responses 30 min after Synacthen. We conclude that where the SST is used to assess the HPA axis, cortisol response at 30 min after intravenous Synacthen should be used.

Two macroprolactinomas presenting with neurological signs.

Macroprolactinomas commonly cause pressure effects on immediate parasellar structures, in particular on the optic chiasm to cause visual field defects. Pressure on more distant brain structures is rarely reported. We describe two massive prolactinomas presenting with neurological signs, including signs of hemiparesis which, to our knowledge, has not been reported previously.

Imaging in endocrinology: use of a potential methodology for audit consensus development.

OBJECTIVE: To explore areas of consensus in the use of imaging techniques in the investigation of endocrine disorders. DESIGN: A postal questionnaire sent to members of the Endocrine Section of the Royal Society of Medicine following a meeting of the Section in January 1993 on Imaging in Endocrinology. SUBJECTS: Fifty-two specialists completed the questionnaire which was sent in the first mailing after the meeting. MEASUREMENTS: Consensus statements were defined as those in which greater than 75% of respondents either agreed or opposed the statement. Majority support or rejection was defined as greater than 50% in favour with less than 25% opposed or vice versa. RESULTS: Many areas of consensus were defined particularly in the field of the use of imaging in the investigation of pituitary disease. The questionnaire highlighted difficulties in obtaining a consensus view on the imaging techniques which should be employed in the investigation of thyroid, parathyroid and pancreatic disorders. CONCLUSION: The results are a useful guide to areas in which further discussion and/or research is required. This methodology could, and we believe should, be applied to other areas of endocrine practice. Such results provide an initial data base to develop national audit guide-lines on the use of imaging techniques in endocrine disorders.

Preliminary observations using endocrine markers of pituitary venous dilution during bilateral simultaneous inferior petrosal sinus catheterization in Cushing's syndrome: is combined CRF and TRH stimulation of value?

OBJECTIVE: We determined whether the measurement of hormones in pituitary blood permits correction for dilution by non-pituitary blood during bilateral simultaneous inferior petrosal sinus blood sampling in Cushing's syndrome. DESIGN: Bilateral simultaneous inferior petrosal sinus blood sampling was performed after combined hCRF and TRH stimulation. Peak ACTH concentrations were corrected for the TSH and PRL inter-sinus ratio, assuming uniform secretion of both hormones into each inferior petrosal sinus. PATIENTS: Eight patients with clinical and biochemical features of Cushing's syndrome. MEASUREMENTS: Basal and stimulated ACTH, TSH and PRL concentrations were measured after bilateral simultaneous inferior petrosal sinus blood sampling and simultaneously from a peripheral forearm vein. RESULTS: Basal central:peripheral ACTH ratio misdiagnosed four of eight patients as having non-pituitary disease. Peak uncorrected ACTH central:peripheral ratio erroneously suggested two of eight patients had non-pituitary disease. ACTH central:peripheral ratio corrected by TSH and PRL correctly predicted pituitary-dependent disease in all eight cases and provided correct lateralization data in four of five patients with a unilateral pituitary microadenoma. CONCLUSION: This study suggests that measuring other hormones in pituitary blood after TRH stimulation can offer a simple and reliable method for correcting for dilution by non-pituitary blood during bilateral simultaneous inferior petrosal sinus blood sampling in Cushing's syndrome.