Association between olfactory function and quality of life in patients with olfactory disorders: a multicenter study in over 760 participants.

BACKGROUND: This cross-sectional, multi-centric study aimed to investigate the differences in quality of life among patients with olfactory dysfunction (OD) of different origin, and to identify factors associated with olfactory-related quality of life (QOL). METHODS: Seven hundred sixty-three adults were recruited from 8 Smell & Taste clinics in Germany, Switzerland, and Austria. Olfactory-related QOL was assessed by the Questionnaire of Olfactory Disorders (QOD). Olfactory function was assessed with the "Sniffin' Sticks" test; self-assessment was performed with visual analog scales. RESULTS: Patients with post-infectious and post-traumatic OD showed poorer olfactory-related QOL than patients with sinonasal and idiopathic OD. The olfactory-related QOL was positively associated with the "Sniffin' Sticks" test score, self-assessed olfactory function, disease duration, and age, with younger olfactory dysfunction patients showing lower QOL. Female patients presented with poorer olfactory-related QOL. In addition, the results showed that self-assessment of olfactory function explained more of the variance in olfactory-related QOL than olfactory function evaluated by the Sniffin’ Sticks test. CONCLUSIONS: In addition to the psychophysical testing results, several factors such as disease cause, disease duration, sex, or self- assessed olfactory dysfunction should be taken into account when assessing the individual severity of the smell loss.

Individual importance of olfaction decreases with duration of smell loss.

BACKGROUND: The personal importance of a lost neurologic - motor or sensory - function in several conditions has been shown to decrease as the afflicted patient becomes accustomed to not having that function. It is unknown how the importance of olfaction changes with duration of olfactory dysfunction (OD). The aim of this study was to evaluate the association between duration of smell loss and individual significance of olfaction, and whether this relationship would be modulated by other factors, such as etiology of smell loss. METHODS: This is a retrospective study including a total 163 subjects with different degrees of olfactory function. Individual significance of olfaction was measured using the Importance of Olfaction Questionnaire (IOQ). Demographics, olfactory function, duration and etiology of OD were evaluated. Group comparisons, bivariate correlations, analyses of variance and multivariate linear regression were applied to detect differences and associations with the outcome measure of IOQ. RESULTS: A significant negative correlation was found between duration of OD and the IOQ. Other important findings include a significantly higher IOQ in patients with posttraumatic- compared to idiopathic OD and in patients with higher aggravation scores compared to the lower aggravation group. Multivariate regression analysis further confirmed that duration of smell loss was independently associated with IOQ. CONCLUSIONS: The duration of smell loss is negatively correlated with the individual importance of olfaction, suggesting that patients develop coping mechanisms for adjusting to OD.

Retronasal olfactory testing using candies sent by post and for screening purposes: a feasibility study.

BACKGROUND: The olfactory system is able to detect external odours through the orthonasal- and internal odours through the retronasal route. Flavour perception strongly relies on the sense of smell and this back route. In contrast to orthonasal, retronasal olfactory tests (ROT) are less frequently applied, although testing should be recommended for several reasons. The aim of the present investigation was to propose a suitable form of ROT for home-testing (and postal distribution) and evaluate a retronasal screening test. METHODOLOGY: Initially, 111 participants were tested using a 27-item version of the Candy Smell Test (CST). Fifty-four participants performed retesting, of which 25 subjects did so in a home-setting being supplied with professionally packed "candy-chains". Seven candies were chosen by means of hit rate differences in normosmics and severely hyposmics/anosmics. The 7-CST is designed in a non-forced-choice fashion with same seven flavours to choose from. RESULTS: For the 27-item CST both groups (subjects performing home-testing and those performing retesting at the clinic) showed highly significant test-rest-reliabilities. The 7-CST was capable of discriminating healthy from diseased subjects when being tested in 116 healthy subjects and 47 patients suffering from olfactory dysfunction. CONCLUSION: The CST is suitable for home-testing and postal distribution. The new 7-item CST can be valuable for rapidly revealing anosmics. These findings help in further standardizing ROT, may encourage rhinologists to more routinely evaluate retronasal olfactory abilities and pave the way for larger epidemiologic studies also in regard to food preferences and nutritional behaviour.

Testing gustatory function using either a forced-choice or a non-forced-choice paradigm - Does it make a difference?

BACKGROUND: Recently more interest is evolving for research on gustatory function, also due to findings of â€extraoral†taste receptors with postulated participation in a pathogen detection network. Also, bitter taste function seems to be reduced in patients with chronic rhinosinusitis. For testing gustatory function â€taste strips†(TS) have been validated in a forced-choice (fc) and a non-forced-choice (nfc) paradigm and used in several studies. Purpose of the investigation was to evaluate possible differences of named modalities. METHODOLOGY: Healthy subjects (n=102) with subjective normal gustatory function and patients (n=30) with potential taste dysfunction were included. All participants were tested twice (using TS in four concentrations of sweet, sour, salty, and bitter taste), either starting with a fc or a nfc paradigm. RESULTS: In tested patients there was a difference between fc and nfc procedure with higher results for bitter in the fc testing procedure, while other qualities did not differ. This effect was also visible in the overall participants with higher scores in the fc procedure for bitter taste. CONCLUSION: TS are valid to be used in a forced and a non-forced choice paradigm, with bitter taste showing slightly higher scores in forced-choice testing. Future investigators with focus on bitter taste perception should be particularly cautious when comparing results in regard to testing procedure.

ANNIVERSARY REVIEW: 50 years since the discovery of bromocriptine.

Ergotism is the long-term ergot poisoning by ingestion of rye or other grains infected with the fungus Claviceps purpurea and more recently by excessive intake of ergot drugs. It has either neuropsychiatric or vascular manifestations. In the Middle Ages, the gangrenous poisoning was known as St. Anthony's fire, after the order of the Monks of St. Anthony who were particularly skilled at treating the condition. In 1917, Prof. Arthur Stoll returned home to Switzerland from Germany, to lead the development of a new pharmaceutical department at Sandoz Chemical Company. Stoll, using the special methods of extraction learned from his work with his mentor Willstetter, started his industrial research work with ergot. He succeeded in isolating, from the ergot of rye, ergotamine as an active principle of an old popular remedy for excessive post-partum bleeding. The success of this discovery occurred in 1918 and was translated into a pharmaceutical product in 1921 under the trade name Gynergen. In subsequent work, Stoll and his team were leaders in identifying the structure of the many other alkaloids and amines produced by Claviceps purpurea This was the cultural background and scientific foundation on which bromocriptine was discovered.

Long-term remission and recurrence rates in Cushing's disease: predictive factors in a single-centre study.

OBJECTIVE: To investigate the early and late outcomes of patients with Cushing's disease (CD) submitted to a neurosurgical procedure as first-line treatment. DESIGN: In this single-centre retrospective case notes study, 131 patients with CD with a minimum follow-up period of 6 years (124 operated by transsphenoidal surgery (TSS) and seven by the transcranial approach) were studied. Apparent immediate cure: post-operative 0900 h serum cortisol level <50 nmol/l; remission: cortisol insufficiency or restoration of 'normal' cortisol levels with resolution of clinical features; and recurrence: dexamethasone resistance and relapse of hypercortisolaemic features. RESULTS: In patients operated by TSS, remission of hypercortisolaemia was found in 72.8% of 103 microadenomas and 42.9% of 21 macroadenomas, with recurrence rates 22.7 and 33.3% respectively with a 15-year mean follow-up (range, 6-29 years). Of 27 patients with microadenomas operated after 1991, with positive imaging and pathology, 93% obtained remission with 12% recurrence. In multivariate analysis, the time needed to achieve recovery of hypothalamo-pituitaryadrenal axis was the only significant predictor of recurrence; all patients who recurred showed recovery within 3 years from surgery: 31.3% of patients had total hypophysectomy with no recurrence; 42% of patients with selective adenomectomy and 26.5% with hemi-hypophysectomy showed recurrence rates of 31 and 13% respectively (χ(2)=6.275, P=0.03). Strict remission criteria were not superior in terms of the probability of recurrence compared with post-operative normocortisolaemia. CONCLUSIONS: Lifelong follow-up for patients with CD appears essential, particularly for patients who have shown rapid recovery of their axis. The strict criteria previously used for 'apparent cure' do not appear to necessarily predict a lower recurrence rate.

Specific electrocardiographic features associated with Cushing's disease.

OBJECTIVE: Hypercortisolaemia is associated with an increased risk of cardiovascular disease (CVD), either through a direct action on the myocardium or by increased traditional cardiovascular risk factors. The aim of this study was to investigate whether the alterations in the ECG in Cushing's disease (CD) are predictable from risk factor analysis alone. DESIGN: In 79 patients with a diagnosis of CD, retrospectively recruited, ECG features [corrected for heart rate QT (QTc), QTc dispersion (QTcd), left ventricular hypertrophy (ECG-LVH), right ventricular hypertrophy (ECG-RVH)], systolic (SBP) and diastolic (DBP) blood pressure were assessed. Biochemical, hormonal (cortisol at 09·00 h or cortisol day curve, CDC) and carbohydrate abnormalities (CHA), history of hypertension and cardiovascular disease were recorded. For comparison reasons, a group of 42 healthy subjects matched for gender, age and body mass index previously subjected to ECG assessment were selected. RESULTS: In patients with CD, we noted the following prevalence: metabolic syndrome 39%, hypertension 81%, CVD 21·5%, hypercholesterolaemia 37%, hypertriglyceridaemia 29%, CHA 41%, but a history of cardiac dysrhythmia was only noted in a single patient. No difference in QTc or QTcd was shown between patients with normal or low potassium levels. QTcd >50 ms was associated with both increased ECG-LVH and ECG-RVH. When compared to the control group, patients had longer QTcd (P < 0·001), more prevalent LVH (P < 0·001) and RVH (P = 0·001), and higher SBP and DBP (P < 0·001), but similar QTc. Both CD and ECG evidence of LVH predicted prolonged QTcd, but the association of CD with a prolonged QTcd was independent of other risk factors, including hypertension. CONCLUSIONS: Prolonged QTcd in association with ECG evidence of LVH appears to be the specific feature of CD. This may be relevant in the choice of medical therapy for CD and for consideration of treatment of the comorbidities that are associated with hypercortisolaemia.

Comparisons in the epidemiology, diagnostic features and cure rate by transsphenoidal surgery between paediatric and adult-onset Cushing's disease.

OBJECTIVE: There are few published comparisons between paediatric and adult-onset Cushing's disease (CD). We compare the epidemiology, diagnostic features and cure rate by transsphenoidal surgery (TSS) in these groups. DESIGN: Retrospective review of patient databases in a single university hospital centre. PATIENTS: Totally, 41 paediatric (mean age 12.3 ± 3.5 years; range 5.7-17.8) and 183 adult (mean age 40 ± 13 years; range 18.0-95.0) patients with CD were investigated. RESULTS: Paediatric CD was characterised by male (63%) and adult CD by a female predominance (79%, P<0.0001). There were small but significant differences in clinical presentation. Biochemical features of CD were comparable except the serum cortisol increase during a CRH test: mean change (105%, n=39) in paediatric and (54%, n=123) in adult subjects (P<0.0001). Macroadenomas were more common in adult (15%, 28/183) than in paediatric (2%, 1/41, P=0.04) CD. Corticotroph microadenomas were more easily visualised by pituitary magnetic resonance imaging (MRI) in adult (76%, 50/66) compared with paediatric (55%, 21/38, P=0.045) CD with poorer concordance of imaging with surgical findings in children (P=0.058). The incidence of ACTH lateralisation by bilateral simultaneous inferior petrosal sinus sampling was comparable in paediatric (76%, 25/33) and adult (79%, 46/58; P=0.95) patients with good surgical concordance in both (82% paediatric and 79% adult). Cure rates by TSS were comparable, with a paediatric cure rate of 69%. CONCLUSION: Several features of paediatric CD are distinct: increased frequency of prepubertal CD in males, the different clinical presentation, the decreased presence of macroadenomas and the frequent absence of radiological evidence of an adenoma on MRI.

AIP mutation in pituitary adenomas in the 18th century and today.

Gigantism results when a growth hormone-secreting pituitary adenoma is present before epiphyseal fusion. In 1909, when Harvey Cushing examined the skeleton of an Irish patient who lived from 1761 to 1783, he noted an enlarged pituitary fossa. We extracted DNA from the patient's teeth and identified a germline mutation in the aryl hydrocarbon-interacting protein gene (AIP). Four contemporary Northern Irish families who presented with gigantism, acromegaly, or prolactinoma have the same mutation and haplotype associated with the mutated gene. Using coalescent theory, we infer that these persons share a common ancestor who lived about 57 to 66 generations earlier.

Repeated colonoscopic screening of patients with acromegaly: 15-year experience identifies those at risk of new colonic neoplasia and allows for effective screening guidelines.

OBJECTIVE: It is suggested that patients with acromegaly have an increased risk of colorectal cancer and pre-malignant adenomatous polyps. However, the optimum frequency with which colonoscopic screening should be offered remains unclear. DESIGN: To determine the optimum frequency for repeated colonoscopic surveillance of acromegalic patients. METHODS: We retrospectively reviewed the case records of all patients with acromegaly seen in our centre since 1992: 254 patients had at least one surveillance colonoscopy, 156 patients had a second surveillance colonoscopy, 60 patients had a third surveillance colonoscopy and 15 patients had a fourth surveillance colonoscopy. RESULTS: The presence of hyperplastic or adenomatous polyps was assessed in all patients, while one cancer was detected at the second surveillance. At the third surveillance, mean (+/-s.d.) serum IGF1 levels (ng/ml) in patients with hyperplastic polyps were significantly higher than those with normal colons (P<0.05). The presence of an adenoma rather than a normal colon at the first colonoscopy was associated with a significantly increased risk of adenoma at the second (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.9-10.4) and at the third (OR 8.8, 95% CI 2.9-26.5) screens. Conversely, a normal colon at the first surveillance gave a high chance of normal findings at the second (78%) or third surveillance (78%), and a normal colon at the second colonoscopy was associated with normality at the third colonoscopy (81%). CONCLUSIONS: Repeated colonoscopic screening of patients with acromegaly demonstrated a high prevalence of new adenomatous and hyperplastic colonic polyps, dependent on both the occurrence of previous polyps and elevated IGF1 levels.

Diagnosis, management and therapeutic outcome in prepubertal Cushing's disease.

OBJECTIVES: Cushing's disease (CD) in prepubertal children is very rare and presents important diagnostic and therapeutic challenges. We report experience of the management of this subpopulation of CD patients. STUDY DESIGN/METHODS: Retrospective patient case note review. RESULTS: Between 1985 and 2008, 17 prepubertal children (13M, 4F), aged 5.7-14.1 years presented to our centre for diagnosis and management of CD. All children had subnormal linear growth and excessive weight gain at presentation. A high proportion (85% of males, 75% of females) had evidence of excessive virilisation. Striae and hypertension were seen in 41% of patients. The investigation with highest sensitivity (100%) for CD was excessive increase of serum cortisol to i.v. CRH (mean increase 113%). Pituitary imaging performed in all the patients showed poor concordance with findings at surgery (31%). In contrast bilateral simultaneous inferior petrosal sinus sampling (BSIPSS), performed in 11/16 subjects showed a high correlation with surgical findings (91%). In 16 patients, transsphenoidal selective adenomectomy (TSS) achieved a cure rate of 44%. However, in the 11 patients who had pre-operative BSIPSS, the cure rate was 64%. Of the 16 patients, 9 patients who were not cured by TSS received external pituitary radiotherapy. CONCLUSIONS: Prepubertal CD had distinctive features with increased frequency in males, abnormal auxology and excessive virilisation. The cortisol response to i.v. CRH administration was particularly exuberant and contributed to diagnosis. BSIPSS was much more helpful than pituitary imaging in localisation of the microadenoma and was associated with improved cure rate by TSS.

Gamma knife radiosurgery: a safe and effective salvage treatment for pituitary tumours not controlled despite conventional radiotherapy.

OBJECTIVE: We report the use of 'gamma knife' (GK) radiosurgery in 25 patients with pituitary adenomas not cured despite conventional therapy, including external beam radiotherapy. PATIENTS AND METHODS: All patients had previously received conventional radiotherapy for a mean of 11.8 years prior to receiving GK; 23 out of 25 had also undergone pituitary surgery on at least one occasion. Seventeen had hyperfunctioning adenomas that still required medical therapy without an adequate biochemical control--ten somatotroph adenomas, six corticotroph adenomas and one prolactinoma, while eight patients had non-functioning pituitary adenomas (NFPAs). RESULTS: Following GK, mean GH fell by 49% at 1 year in patients with somatotroph tumours. Serum IGF1 fell by 32% at 1 year and by 38% at 2 years. To date, 80% of the patients with acromegaly have achieved normalisation of IGF1, and 30% have also achieved a mean GH level of <1.8 ng/ml correlating with normalised mortality. A total of 75% NFPAs showed disease stabilisation or shrinkage post GK. The patient with a prolactinoma showed a dramatic response: 75% reduction in prolactin at 2 years, with a marked shrinkage on magnetic resonance imaging. The results in corticotroph adenomas were variable. Prior to GK, 72% of the patients were panhypopituitary, and 42% of the remainder have developed new anterior pituitary hormone deficiencies to date. No other adverse events have been detected at a mean follow-up of 36.4 months. CONCLUSIONS: These data indicate that GK is a safe and effective adjunctive treatment for patients with NFPAs and acromegaly not satisfactorily controlled with surgery and radiotherapy.

The prevalence and characteristic features of cyclicity and variability in Cushing's disease.

OBJECTIVE: Cyclical Cushing's syndrome may render the diagnosis and management of Cushing's disease difficult. The aim of the present study was to investigate the prevalence of cyclicity and variability in patients with Cushing's disease, and to identify putative distinctive features. DESIGN: Retrospective case-note study. METHODS: We analysed the case records of 201 patients with Cushing's disease in a retrospective case-note study. Cyclicity was considered as the presence of at least one cycle, defined as a clinical and/or biochemical hypercortisolaemic peak followed by clinical and biochemical remission, followed by a new clinical and/or biochemical hypercortisolaemic peak. The fluctuations of mean serum cortisol levels, as assessed by a 5-point cortisol day curve, defined the variability. RESULTS: Thirty (14.9%; 26 females) patients had evidence of cyclicity/variability. 'Cycling' patients were older but no difference in sex or paediatric distribution was revealed between 'cycling' and 'non-cycling' patients. The median number of cycles was two for each patient, and 4 years was the median intercyclic period. A trend to lower cure rate post-neurosurgery and lower adenoma identification was observed in 'cycling' compared with 'non-cycling' patients. In multivariate analysis, older patients, longer follow-up, female sex and no histological identification of the adenoma were associated with an increased risk of cyclic disease. CONCLUSIONS: This large population study reveals that cyclicity/variability is not an infrequent phenomenon in patients with Cushing's disease, with a minimum prevalence of 15%. Physicians should be alert since it can lead to frequent problems in diagnosis and management, and no specific features can be used as markers.

Safety of GH replacement in hypopituitary patients with nonirradiated pituitary and peripituitary tumours.

BACKGROUND: Published data suggest that growth hormone replacement (GHR) may be given safely to patients with hypopituitarism consequent upon a pituitary/peripituitary tumour. However, a preponderance of patients treated with external pituitary irradiation were included. OBJECTIVE: To assess the safety of GHR in nonirradiated pituitary/peripituitary tumour. DESIGN: Prospective audit. SETTING: Tertiary university referral centre. PATIENTS: We imaged prospectively the pituitary glands of 48 patients (18 males; mean age 51.6 years range 21-77) who had adult onset growth hormone deficiency (AO-GHD) after appropriate treatment for a pituitary/peripituitary tumour but who did not receive external pituitary irradiation. INTERVENTION: All patients were treated with a dose titration regimen of GH to maintain serum IGF-1 between the median and upper end of the age-related reference range. Pituitary surveillance imaging was performed prior to the commencement of GHR, at 6-12 months and then yearly. For patients with secretory tumours, biochemical markers (cortisol and prolactin) were used as evidence of tumour recurrence. RESULTS: 48 patients with median follow up since commencement of GHR was 38 months (range 9-104). Three patients were judged to have an apparent increase in tumour volume and/or marker, although only one was thought to be possibly GH related--a patient with a cystic chromophobe adenoma who demonstrated a marginal increase in residual tumour volume 4 years after commencement of GHR. CONCLUSION: These data add to the growing body of evidence for the safety of GHR in hypopituitary patients consequent upon pituitary/peripituitary mass lesions and represents the first reported series in a heterogeneous group of nonirradiated patients.

Role of fasting plasma glucose, glycated haemoglobin and homeostatic model assessment in the detection of glucose intolerance in adult hypopituitary patients during growth hormone replacement therapy.

AIMS: This study was designed to determine the sensitivity and specificity of conventional criteria for diagnosis of impaired glucose tolerance (IGT) in a high-risk population of GH-treated GH deficient (GHD) adults. METHODS: 33 hypopituitary GHD patients with HbA(1c) >5.1% and 13 gender- and age-matched control GHD patients were selected. Oral glucose tolerance test (OGTT), fasting plasma glucose (FPG), HbA(1c), and homeostatic model assessment (HOMA) parameters were determined in all patients. Receiver operator characteristic curves were used to determined sensitivity and specificity for the detection of glucose intolerance as defined by plasma glucose >7.8 mmol/l at 120 min during OGTT. RESULTS: Sensitivity and specificity for this purpose for HbA(1c) (>5.1%) were 89 and 17%; for FPG (>5.5 mmol/l): 78 and 67%; for FPG (>6.1 mmol/l): 56 and 89%; for HOMA-derived beta-cell function (betaCF) (<40%): 78 and 58%; for HOMA-derived insulin sensitivity (IS) (<70%): 11 and 89%, and for betaCF-IS hyperbolic product (betaCF-IS) (<54%): 89 and 75%, respectively. CONCLUSIONS: This study shows that FPG (>5.5 mmol/l) and betaCF-IS have high sensitivity and relatively high specificity for the detection of IGT and confirms that measurement of FPG or calculation of betaCF-IS provides appropriate safety surveillance in hypopituitary patients on GH replacement.

Abnormal puberty in paediatric Cushing's disease: relationship with adrenal androgen, sex hormone binding globulin and gonadotrophin concentrations.

OBJECTIVE: Paediatric Cushing's disease is frequently associated with abnormal puberty. We addressed the hypothesis that prepubertal patients show excessive virilization and pubertal patients show suppression of LH and FSH secretion. DESIGN AND MEASUREMENTS: Serum androstenedione (A4), dehydroepiandrosterone sulphate (DHEAS), testosterone (T), and sex hormone binding globulin (SHBG) were determined at diagnosis and converted to standard deviation scores. LH, FSH concentrations were also determined. Severity of CD was assessed from the sleeping midnight cortisol concentration. Puberty was staged and excessive virilization defined as advance in pubic hair stage for breast stage or testicular volume (TV). PATIENTS: Twenty-seven CD patients (17 male, 10 female), median age 13.4 years (range 5.9-17.8) were studied. RESULTS: In the CD group as a whole, A4, DHEAS, T standard deviation scores (SDS) values were normal. SHBG SDS values (n = 19) were low (median -1.93, -4.32-0.86) correlating with BMI (r = -0.49). A4, DHEAS, T, SHBG, LH and FSH did not correlate with midnight cortisol, but A4 and T SDS correlated with ACTH at 09.00 h (both r = 0.51). Thirteen patients (11 male, 2 female) had excessive virilization with increased A4 (P = 0.033), DHEAS (P = 0.008), testosterone (P = 0.033) and decreased SHBG (P = 0.004) compared with subjects without excessive virilization. Pubertal boys (TV > or = 4 ml) (n = 7) and girls (breasts > or = stage 2) (n = 8) had low median LH and FSH. Boys had an LH concentration of 1.2 mU/l (0.3-3.5), FSH, 0.9 mU/l (0.2-6.4) and median T SDS, -1.95 (-3.8-4.65), while girls had an LH concentration of 1 mU/l (0.3-7.4). CONCLUSIONS: Many patients had abnormal puberty and excessive virilization associated with increased adrenal androgens and decreased SHBG. Pubertal patients had low LH and FSH suggesting impaired pituitary-gonadal axis function.

Long-term anterior pituitary function in patients with paediatric Cushing's disease treated with pituitary radiotherapy.

BACKGROUND/OBJECTIVE: Pituitary radiotherapy (RT) is an effective second-line treatment for paediatric Cushing's disease (CD). Although the short-term effects of pituitary RT are well documented, there are less data on possible long-term sequelae. We report the long-term anterior pituitary function in a cohort of paediatric CD patients treated with pituitary RT. PATIENTS AND METHODS: Between 1983 and 2006, 12 paediatric CD patients (10 males and 2 females) of mean age 11.4 years at diagnosis (range 6.4-17.4) underwent second-line pituitary RT (45 Gy in 25 fractions), following unsuccessful transsphenoidal surgery. Out of 12, 11 patients were cured by RT (cure interval 0.13-2.86 years) defined by mean serum cortisol of <150 nmol/l on 5-point day curve and midnight sleeping cortisol of <50 nmol/l. Long-term data are available for six male patients, who received RT at the age of 7.0-17.6 years. The mean follow-up from the completion of RT was 10.5 years (6.6-16.5). RESULTS: At a mean of 1.0 year (0.11-2.54) following RT, GH deficiency (peak GH <1-17.9 mU/l) was present in five out of six patients. On retesting at a mean of 9.3 years (7.6-11.3) after RT, three out of four patients were GH sufficient (peak GH 19.2-50.4 mU/l). Other anterior pituitary functions including serum prolactin in five out of six patients were normal on follow-up. All the six patients had testicular volumes of 20-25 ml at the age of 14.5-28.5 years. CONCLUSION: This series of patients illustrates the absence of serious long-term pituitary deficiency after RT and emphasises the importance of continued surveillance.

Growth hormone deficiency and replacement in patients with treated Cushing's Disease, prolactinomas and non-functioning pituitary adenomas: effects on body composition, glucose metabolism, lipid status and bone mineral density.

BACKGROUND/AIMS: This study was designed to determine whether previous Cushing's disease (CD) or prolactinoma (PRL) could exert adverse effects additional to those of growth hormone (GH) deficiency as a consequence of variable degrees of prior hypogonadism or hypercatabolism. We report the effects of 5 years GH treatment in 124 GH deficiency adults; 42 patients with non-functioning pituitary adenomas (NFPA), 43 with treated PRL and 39 with treated CD. METHODS: Fasting plasma glucose, HbA(1c), lipoprotein profile, anthropometry and bone mineral density (BMD) were measured at baseline, 6 months and annually up to 5 years. RESULTS: Mean body mass index remained unchanged in the PRL group and tended to increase in the NFPA group. In contrast, body mass index decreased in the CD group. Decreases in waist and waist/hip ratio were seen in all groups at 6 months. Decreases in total cholesterol and low-density lipoprotein cholesterol were seen in all groups and remained sustained at 5 years. Plasma glucose and HbA(1c) increased at 6 months. Subsequently, plasma glucose returned to baseline values at 5 years; in contrast, HbA(1c )remained unchanged at the end of the study. Baseline lumbar spine and hip BMD were lower in the PRL and CD groups than in the NFPA group, decreased over 1 year in all groups and subsequently increased by 2 years in NFPA with a subsequent increase in lumbar spine BMD in PRL and CD groups delayed to 3-5 years. CONCLUSIONS: Baseline characteristics and response to GH replacement are qualitatively similar in NFPA, PRL and CD patients. Because improvements in BMD occur later in PRL and CD patients, an extended trial of GH therapy may be indicated in those patients who were commenced on GH therapy as an additional treatment for reduced BMD.