Cushing's syndrome is characterized by excessive elevation of glucocorticoid concentrations. In rare cases, the treatment of Cushing's syndrome may result in unmasking or aggravation of diseases responsive to glucocorticoid medication. We report two cases of sarcoidosis following Cushing's syndrome. A 43 year-old male developed cutaneous sarcoidosis and mediastinal lymphadenopathy after resection of an ACTH-secreting pituitary microadenoma. A 32 year-old female showed cutaneous sarcoidosis, arthralgia, mediastinal lymphadenopathy and elevation of angiotensin-converting enzyme and interleukin 2-receptor concentrations after traumatic adrenal bleeding, which ceased formerly undiagnosed hypercortisolism caused by an adrenal adenoma. Sarcoidosis seems to be a rare sequel following the treatment of hypercortisolism. Skin affections were present and suggestive for the diagnosis in all reported cases. As some cases are probably missed when skin affections are lacking, a more frequent evaluation of patients after Cushing's syndrome for the possible diagnosis of sarcoidosis might be necessary.

Imaging of the adrenals by endoscopic ultrasound (EUS) is a valuable technique for detection and localization of adrenal lesions, but endosonomorphological tumor distinction remains difficult. In this single-center study, the amount of blood flow in common adrenal lesions, such as adrenal adenomas, adrenal hyperplasia, and pheochromocytomas, was visualized by color-coded duplex EUS (CD-EUS) and was retrospectively analysed. Therefore, we reviewed our EUS database to evaluate and correlate the perfusion patterns of common adrenal lesions with histologically confirmed diagnosis, possible malignancy, and endosonomorphological features such as echogeneity, echostructure, and tumor size. CD-EUS was performed using an endosonoscope Pentax FG 32 UA with a longitudinal 7.5 MHz sector array and Hitachi EUB 525 ultrasound system. In 38 consecutive patients (male=19; female=19; age: mean 53±16 yr SD), perfusion patterns of 46 histologically confirmed adrenal, para- or extra-adrenal lesions of adrenal origin (adenoma: no.=20; nodular hyperplasia: no.=11; pheochromocytoma: no.=15; diameter 26±15 mm, range 6–70 mm) were analyzed and classified semiquantitatively as “not” (no.=24), “slightly” (no.=12), “moderately” (no.=4) or “highly” (no.=6) hypervascularized. Compared to adenomas (p=0.003) and nodular hyperplasia (p=0.047), pheochromocytomas showed a significantly higher grade of perfusion. There was no relationship between perfusion patterns and localization of pheochromocytomas (adrenal: 8; paraadrenal: 3; extra-adrenal: 4). Vascularization was not statistically associated with tumor echogeneity, echostructure, malignancy or tumor size. CD-EUS is an additional tool for adrenal endosonographic tumor distinction and seems to improve the endosonographic detection of pheochromocytomas by visualization of hypervascularization. As an overlap of perfusion patterns exists, CD-EUS findings must be interpreted in the context of clinical, laboratory and chemical results.

Objective GH acts through the GH receptor (GHR). The GHR gene contains a genetic polymorphism caused by a deletion of exon 3 (d3), with high frequency in the normal population. There is a continuing controversy whether the presence or absence of the exon 3 deletion (d3+ vs. d3-) affects the effect of GH in human growth.Design, patients and measurements For 144 patients with idiopathic isolated GH deficiency (IGHD, n = 72) or multiple pituitary hormone deficiency (MPHD, n = 72), amplification of the region around exon 3 of the GHR gene was performed. Clinical data and response to GH treatment were compared between GHR d3+ and d3- IGHD and MPHD patients born either small for gestational age (SGA) or appropriate for gestational age (AGA). IGHD patients born SGA had a significantly higher d3+frequency (82%) than IGHD patients born AGA (35%, P = 0.006). Within the group of IGHD patients born SGA, d3- patients showed a slightly better spontaneous catch up growth before start of GH treatment than d3+ patients (1.1 +/- 1.1 SD vs. 0.6 +/- 1.1 SDS, P = 0.040) There was no difference in patients first year's response to GH treatment between GHR d3+ and d3- patients.Conclusions In IGHD and MPHD patients, response to GH treatment was independent of GHR genotype. GHR-d3 was significantly more frequent among IGHD patients born SGA. As we are the third to report an association between birth size and GHR d3 status, it is conceivable that the GHR-d3 might affect prenatal growth in IGHD patients by a yet unknown mechanism.

OBJECTIVE Hypothalamic-pituitary insufficiency may have diverse causes. The aim of this study was to determine the incidence of hypothalamic-pituitary insufficiency in patients with previous infectious diseases of the central nervous system (CNS) of different etiologies and mild-to-moderate clinical course. DESIGN Patient series. Basal and stimulated (insulin tolerance test) pituitary function testing was performed in 19 patients with previous neuroborreliosis, encephalitis, or meningitis following an interval of between 10 and 56 months (mean 26.1+/-13.1 months) after the acute event. RESULTS Four patients (21%; two males, two females) showed an isolated corticotropic insufficiency (peak cortisol <181.25 microg/l during the insulin tolerance test). Two patients (11%, males) showed borderline gonadotropic insufficiency (basal testosterone between 2.4 and 3.0 microg/l). No patient had somatotropic or thyrotropic insufficiency or evidence for diabetes insipidus; all had prolactin concentrations within the reference range. CONCLUSIONS Hypothalamic-pituitary dysfunction and especially isolated corticotropic insufficiency may develop in a relevant proportion of patients after infectious diseases of the CNS.

OBJECTIVE:Adrenal lesion is one of the features of multiple endocrine neoplasia type 1 (MEN1). This study aimed to assess prevalence, natural course and clinical relevance of small adrenal lesions without clinical symptoms, endocrine activity, or mechanical problems and thus without clear indication for surgical therapy by endoscopic ultrasound (EUS).DESIGN AND METHODS:Forty-nine patients with familial MEN1 were studied. Twenty-seven of these with adrenal lesions were detected by EUS and at least two performed EUS examinations were included into a subgroup where changes in adrenal morphology were studied by measuring changes in the largest diameter of the dominant adrenal tumour.RESULTS:EUS detected adrenal lesions in 36 (73%) patients: 6 (12%) plump adrenals, 17 (35%) nodular hyperplasia, 12 (24%) adenomas and 1 (2%) cyst. Bilateral adrenal lesions were detected in 17 patients and unilateral in 19 patients. A change in the largest tumour diameter was found to be for nodular hyperplasia -0.02+/-1.41% per month (range -2.56 to 4.58%) and for adenomas -0.61+/-1.95% per month (range -6.25 to 1.15%). One patient had an adrenal cyst with significant growth. There was no evidence of carcinoma or metastatic disease during the study.CONCLUSIONS:The prevalence of adrenal lesions in MEN1 is higher than that reported earlier. Except one cystic lesion, no significant change in the tumour size was observed over a mean observation period of more than 2 years. In a typical situation, small adrenal lesions in MEN1 seem to be constant in their morphology.

Objectives: The exon 3-deleted/full-length growth hormone receptor (d3/fl GHR; 5p13–12) polymorphism has recently been associated with responsiveness to growth hormone (GH) therapy in idiopathic-short-stature-, small-for-gestational-age-, Turner- and GH-deficient children. The GHRd3-allele was accompanied by an increased responsiveness to GH.

Patients with multiple endocrine neoplasia type 1 (MEN1) represent among cancer patients a particular group of hereditary tumour syndrome with a long duration of disease and multiple follow-ups. MEN1 is characterized by predisposition mainly to tumours of the parathyroid glands and (enteropancreatic) neuroendocrine tumours but also involvement of anterior pituitary, adrenals and other endocrine glands. Only one report regarding quality of life (QoL) in these patients is available so far (Berglund et al., Fam Cancer 2003). Patients and Methods: 23 patients (13 males, 10 females, age range 23–67yrs) with MEN1, followed up by the interdisciplinary team (internists and surgeons) in our university hospital. Patients answered three questionnaires: the Nottingham Health Profile (NHP – a generic healthy survey), the questionnaire for Quality of life – Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA – designed to evaluate adult patients with growth hormone deficiency) and the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Version 3.0– used to asses the health related quality of life in cancer patients (22 patients). The results for the NHP and the EORTC QLQ-C30 were matched to reference data published for theses questionnaires for the German population. Differences ≥ +2 SD (standard deviation) were defined as pathological, ≤+1 as normal and between +1SD and +2 SD as marginal/intermediate. Results: Most pathological scorings in the NHP were for energy lost (26%) and emotional reactions (22%). Only 13% reported pains. 26% of patients showed low QoL as evaluated with the QoL-AGHDA (47% of the studied patients hat pituitary involvement but none of them pituitary hormones deficiencies). Scorings on functional scales of the EORTC QLQ-C30 were comparable and higher for the cognitive and role scales (better QoL), the lowest ratings were achieved for the social, emotional and physical scales. On the symptoms scale more problems were reported with fatigue (41%), less with pain and with nausea/vomiting. The global health/QoL scale reflected only in 14% patients pathological results, but indicated marginal results in 32%. Conclusions: Patients with MEN1 perceives their global/health-related QoL as reduced but still relatively good; items as energy lost/fatigue rises as the most important aspects, probably influencing physical, emotional and social functioning.

Over 90 percent of neuroendocrine tumors, including nonfunctioning pancreatic tumors are expressing somatostatin receptors.

MEN1 is characterised by predisposition mainly to tumors of the parathyroid glands and enteropancreatic neuroendocrine tumors (NET). Pituitary involvement was underestimated.

Objective.- Genetic factors play an expanding role in understanding growth hormone (GH) disorders, therefore the German KIMS Pharmacogenetics Study was initiated with the aim of genotyping various GH-/IGF-I-axis-related genes of GH-deficient adult patients to investigate genotype:phenotype relationships and response to GH therapy.Patients and methods: 129 consecutively enrolled GH-deficient adult patients were genotyped for variant 1 (VI) of the alternatively spliced noncoding exons in the 5'-untranslated region and for the nine coding exons of the GH receptor (GHR) gene, which obviously play a striking role in the function of the GH-IGF-I-axis. After detection of a heterozygous, non-synonymous mutation R179C in exon 6 in one single patient with acquired GH-deficiency (GHD) in late adulthood, analysis of her clinical data followed, leading to the diagnosis of mild short stature (-1.5 SID). For further endocrine evaluation, five pituitary stimulation tests (arginine) of this patient were statistically compared to stimulation tests (arginine) of ten GH-deficient control patients, retrospectively.Results: The formerly in patients with Laron syndrome and idiopathic short stature reported mutation R179C leads to an amino acid change from an arginine residue (codon CGC) to a cysteine residue (codon TGC) in position 179 of the extracellular domain of the GHR. Statistical analysis revealed significant decreased IGF-I/GHO ratio (p = 0.004) and IGF-I/GH(max) ratio (p = 0.001) of the index patient compared to the control patients, implying growth hormone resistance of the index patient at the level of the GHR according to the detected R179C mutation.Conclusions: This study reports on the unusual case of a patient with mild short stature, who acquired GHD in late adulthood due to a non-secreting pituitary adenoma and get additionally diagnosed for pre-existing growth hormone insensitivity due to a formerly in two short statured patients described, single, heterozygous, non-synonymous mutation in the GHR. Our findings support the theory that heterozygous mutations in the GHR gene can have mild phenotypical consequences. (c) 2007 Elsevier Ltd. All rights reserved.

A variety of conditions can cause hypercalcemia, primary hyperparathyroidism (pHPT) and malignancy account for 80 to 90% of cases. The history, physical examination, chest X-rays, and laboratory assessment will provide the correct diagnosis with an accuracy of 95%. Adding measurement of intact parathyroid hormone (PTH) will increase the accuracy to 99%. In patients with underlying malignancy, elevation of serum calcium is most often caused by hypersecretion of PTH-related peptide (PTHrP). In the absence of malignancy or increased PTHrP and PTH in serum, stimulation of bone resorption (e.g. multiple myeloma) and unrecognized calcium intake in the face of renal insufficiency (as in milk-alkali-syndrome) or vitamin D intoxication are amongst the most common causes. We describe the case of a 44 year old iranian women, who first presented with acute renal failure. She reported generalized osseous pain. Calcium levels were decreased to 4.2 mmol/L (Phosphat 2.8 mmol/L). PTH was suppressed and PTHrP as well as Vitamine- D-metabolites were lowered. Parameters for stimulation of bone resorption were dramatically elevated. Bone x-ray and repeated bone scintigraphy showed diffuse signs of considerably activated bone metabolism without focal accentuation. Consecutive substitution of vitamine D and bisphosphonates resulted in a minimal reduction of bone metabolism, but significant improvement of pain. Subsequently three bone biopsies were obtained, that showed changes compatible with pHPT or secretion of PTHrP. Laboratory values could not confirm this suspected diagnosis. An activation of bone metabolism by PTHrP or aberrant PTH undetected by our assay, could not be excluded. Repeated laboratory and radiological examinations revealed no signs of tumor growth or systemical malignancy at any time. Other causes including sarcoidosis, hyperthyroidism, M. Paget, thiacides, famial hypocalciuric hypercalcemia, vitamine D intoxication, drugs or milk-alkali-syndrome could be excluded. Despite an extensive diagnostic work-up, the cause of hypercalcemia in this patient remained unclear.

Endoscopic ultrasound (EUS) enables detection and localization of pancreatic neuroendocrine tumours. Even small tumours down to a diameter of 1-2 mm can be visualized. Since such small tumours usually cannot be detected by computed tomography (ct), magnetic resonance imaging (mri) and somatostatin receptor scintigraphy (srs), and experience with EUS imaging is limited, there is no clear evidence for clinical management in multiple endocrine neoplasia type 1 (MEN1). Knowledge about the natural course of growth and metastatic distribution is mandatory to come to appropriate clinical decisions and guidelines. This prospective study was aimed to assess the natural course of small (<15 mm) neuroendocrine pancreatic tumours without clinical symptoms due to endocrine activity or mechanical problems and without clear indication for surgical therapy in MEN1 by EUS. A total of 82 asymptomatic tumours<15 mm (5.9+/-3.2 mm diameter at baseline) in 20 patients with MEN1-disease (8 female/12 male, 43+/-13 years) were studied over a period of 20+/-12 months (33.8 patient years, 106.7 tumour years) by EUS. Change in largest diameter of each tumour and annual tumour incidence rate in the patients' cohort were calculated. Increase of largest tumour diameter was found to be 1.3+/-3.2% per month, annual tumour incidence rate 0.62 new tumours per patient year. In one patient, rapid progressive pancreatic manifestation of MEN1 was observed. There was no evidence in ct and/or srs and/or mri for metastatic disease in all patients. Only 4/84 (4.8%) pancreatic tumours could be visualized by computed tomography, 5/79 (6.3%) by somatostatin receptor imaging and 4/39 (10.3%) by magnetic resonance imaging. Small asymptomatic neuroendocrine pancreatic tumours in MEN1 usually seem to grow slowly. Annual tumour incidence rate is low. However, faster growing tumours and patients with rapidly progressive disease can be observed. Risk for obvious metastatic disease from asymptomatic neuroendocrine pancreatic tumours<15 mm in MEN1 seems to be low.

OBJECTIVEThe drugs most commonly used to treat diabetes mellitus are sulfonylureas, biguanides and insulin. The most serious effects seen in overdose with these agents are hypoglycemia or lactic acidosis which may be fatal or cause cerebral defects. The present investigation analyzes inquiries made to a regional poisons unit involving overdoses with sulfonylureas, biguanides and insulin.PATIENTS AND METHODSA total of 218,070 made inquiries between 1995 and 2004 were evaluated. The inquiries were received by telephone and a standardized questionnaire was sent subsequently to the physicians calling for follow-up information. The cases were analyzed with regard to gender, age, etiology, symptoms and clinical outcome.RESULTS263 inquiries concerning sulfonylureas (48.3% female, 49.4% male, 2.3% sex unknown, average age 39.1 +/- 26.8 years), 172 concerning biguanides (60.5% female, 37.2% male, 2.3% sex unknown, average age 41.5 +/- 24.1 years), and 191 concerning insulin (53.9% female, 41.9% male, 4.2% sex unknown, average age 44.6 +/- 16.7) were made. In cases involving sulfonylureas, the etiology was deliberate self-poisoning in 62.7% and accidental in 31.9% (biguanides 60.5% and 29.1%, insulin 85.3% and 9.4%). Using the Poisoning Severity Score, no symptoms were observed in 41.4% of the patients with sulfonylurea overdose (biguanides 40.1%, insulin 22.5%), minor symptoms in 37.6% (biguanides 32.6%, insulin 33.5%), major symptoms in 14.4% (biguanides 13.4%, insulin 26.2%) and serious symptoms in 4.6% (biguanides 12.2%, insulin 14.7%). Returned questionnaires reporting clinical outcomes showed that a full recovery occurred in most patients (sulfonylureas 97.4%, biguanides 93.0%, insulin 94.4%), cerebral defects persisted in 1.8% of the cases involving sulfonylureas (biguanides 1.5%, insulin 2.4%), and that 0.9% of the patients with sulfonylurea overdose died (biguanides 6.1%, insulin 3.6%).CONCLUSIONSSulfonylureas were the most frequently observed medication in cases of overdose with antidiabetic agents. Insulin overdose caused the highest number of major and serious symptoms. Overdose with biguanides led to the most deaths.

History and admission findings: A 38-year-old woman presented with symptoms suggesting Cushing's syndrome 17 years after surgery (hysterectomy, ovarectomy, partially liver resection, right adrenalectomy) and radiatio of a mature ovarian teratoma with hepatic and peritoneal metastases. Main symptom was facial oedema and redness, initially falsely diagnosed as purulent maxilla bone infection.

Annual incidence of acromegaly is three to four per million people. The mean age at diagnosis is between 40 to 45 years. Apart from rare cases, acromegaly is caused by somatotroph adenoma of the anterior pituitary. Most pituitary tumors are sporadic, although a few occur with familial aggregation.

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

Bone biopsy is a diagnostic procedure restricted to untypical, unclear and complicated cases in evidence-based guidelines on diagnosis and treatment of osteoporosis. Its relevance has been a topic of recent controversial discussion. This study was performed to evaluate its role and relevance in routine use. A total of 99 horizontal transiliac bone biopsies performed over a time period of 14 years because of an osteological indication in one single centre were analysed, which reflects that bone biopsy followed about 0.003% of patients' consultations. Bone biopsies were indicated for osteoporotic males (n=63) and premenopausal osteoporotic females (n=18) without endocrine abnormality and normal immunofixation (serum and urine), suspected systemic/malignant disease such as mastocytosis, osteogenesis imperfecta, non-secreting plasmocytoma, metastatic infiltration (n=16) and decreasing bone mineral density under anti-osteoporotic treatment (n=2). The most frequent diagnoses besides osteoporosis were normal histology, borderline finding towards mild osteoporosis, and osteoporomalacia with relevant osteoidosis. In some cases, pathological findings in bone marrow were detected. In most cases (82/99), bone biopsy led to consequences in medical treatment. Following histopathological diagnosis, 16 patients did not receive any anti-osteoporotic treatment. In six patients, further diagnostic procedures were initiated because of bone histology. Bone biopsy was well tolerated and complications were rare and mild. In conclusion, despite all progress in non-invasive diagnostic procedures for metabolic bone diseases such as osteoporosis, there remains a small but significant subset of patients who may benefit from inclusion of bone biopsy into the diagnostic procedure.