Prednisolone is associated with a worse bone mineral density in primary adrenal insufficiency.

CONTEXT: Patients with primary adrenal insufficiency (PAI) or congenital adrenal hyperplasia (CAH) receive life-long glucocorticoid (GC) therapy. Daily GC doses are often above the physiological cortisol production rate and can cause long-term morbidities such as osteoporosis. No prospective trial has investigated the long-term effect of different GC therapies on bone mineral density (BMD) in those patients. OBJECTIVES: To determine if patients on hydrocortisone (HC) or prednisolone show changes in BMD after follow-up of 5.5 years. To investigate if BMD is altered after switching from immediate- to modified-release HC. DESIGN AND PATIENTS: Prospective, observational, longitudinal study with evaluation of BMD by DXA at visit1, after 2.2 ± 0.4 (visit2) and after 5.5 ± 0.8 years (visit3) included 36 PAI and 8 CAH patients. Thirteen patients received prednisolone (age 52.5 ± 14.8 years; 8 women) and 31 patients received immediate-release HC (age 48.9 ± 15.8 years; 22 women). Twelve patients on immediate-release switched to modified-release HC at visit2. RESULTS: Prednisolone showed significantly lower Z-scores compared to HC at femoral neck (-0.85 ± 0.80 vs -0.25 ± 1.16, P < 0.05), trochanter (-0.96 ± 0.62 vs 0.51 ± 1.07, P < 0.05) and total hip (-0.78 ± 0.55 vs 0.36 ± 1.04, P < 0.05), but not at lumbar spine, throughout the study. Prednisolone dose decreased by 8% over study time, but no significant effect was seen on BMD. BMD did not change significantly after switching from immediate- to modified-release HC. CONCLUSIONS: The use of prednisolone as hormone replacement therapy results in significantly lower BMD compared to HC. Patients on low-dose HC replacement therapy showed unchanged Z-scores within the normal reference range during the study period.

BclI polymorphism of the glucocorticoid receptor and adrenal crisis in primary adrenal insufficiency.

CONTEXT: Patients with primary adrenal insufficiency (PAI) or congenital adrenal hyperplasia (CAH) are at a high risk of adrenal crisis (AC). Glucocorticoid sensitivity is at least partially genetically determined by polymorphisms of the glucocorticoid receptor (GR). OBJECTIVES: To determine if a number of intercurrent illnesses and AC are associated with the GR gene polymorphism BclI in patients with PAI and CAH. DESIGN AND PATIENTS: This prospective, longitudinal study over 37.7 ± 10.1 months included 47 PAI and 25 CAH patients. During the study period, intercurrent illness episodes and AC were documented. RESULTS: The study period covered 223 patient years in which 21 AC occurred (9.4 AC/100 pat years). There were no significant differences between BclI polymorphisms (CC (n = 29), CG (n = 34) and GG (n = 9)) regarding BMI, hydrocortisone equivalent daily dose and blood pressure. We did not find a difference in the number of intercurrent illnesses/patient year among BclI polymorphisms (CC (1.5 ± 1.4/pat year), CG (1.2 ± 1.2/pat year) and GG (1.6 ± 2.2/pat year)). The occurrence of AC was not significantly different among the homozygous (GG) genotype (32.5 AC/100 pat years), the CC genotype (6.7 AC/100 pat years) and the CG genotype (4.9 AC/100 pat years). Concomitant hypothyroidism was the highest in the GG genotype group (5/9), compared to others (CC (11/29) and CG (11/34)). CONCLUSIONS: Although sample sizes were relatively small and results should be interpreted with caution, this study suggests that the GR gene polymorphism BclI may not be associated with the frequencies of intercurrent illnesses and AC.

Reduction in daily hydrocortisone dose improves bone health in primary adrenal insufficiency.

OBJECTIVE: Individuals with primary adrenal insufficiency (PAI) or congenital adrenal hyperplasia (CAH) receive life-long glucocorticoid (GC) replacement therapy. Current daily GC doses are still higher than the reported adrenal cortisol production rate. This GC excess could result in long-term morbidities such as osteoporosis. No prospective trials have investigated the long-term effect of GC dose changes in PAI and CAH patients. METHODS: This is a prospective and longitudinal study including 57 subjects with PAI (42 women) and 33 with CAH (21 women). Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry at baseline and after 2 years. Subjects were divided into three groups (similar baseline characteristics) depending on changes in daily hydrocortisone equivalent dose (group 1: unchanged 25.2±8.2  mg (mean±S.D., n=50); group 2: increased 18.7±10.3 to 25.9±12.0  mg (n=13); group 3: decreased 30.8±8.5 to 21.4±7.2  mg (n=27)). RESULTS: Subjects in group 1 showed normal lumbar and femoral Z-scores which were unchanged over time. Group 2 subjects showed a significant decrease in femoral neck Z-scores over time (-0.15±1.1 to -0.37±1.0 (P<0.05)), whereas group 3 subjects showed a significant increase in lumbar spine and hip Z-scores (L1-L4: -0.93±1.2 to -0.65±1.5 (P<0.05); total hip: -0.40±1.0 to -0.28±1.0 (P<0.05)). No changes in BMI over time were seen within any group. Reduction in GC dose did not increase the risk of adrenal crisis. CONCLUSION: This study demonstrates for the first time that cautious reduction in hydrocortisone equivalent doses leads to increases in BMD, whereas dose increments reduced BMD. These data emphasize the need for the lowest possible GC replacement dose in AI patients to maintain health and avoid long-term adverse effects.

Palliative treatment of uncontrollable hypercalcemia due to parathyrotoxicosis: denosumab as rescue therapy.

UNLABELLED: Parathyroid carcinoma is a rare disease leading to severe hypercalcemia due to hyperparathyroidism. Surgery is the primary treatment option. A more progressive form of the disease is characterized by parathyrotoxicosis, and subsequent hypercalcemia is the most common cause of death. We report a case presenting with severe hypercalcemia due to parathyrotoxicosis from parathyroid carcinoma treated for the first time using the monoclonal antibody denosumab as a rescue therapy and present long-term follow-up data. The 71-year-old patient presented with severe hypercalcemia due to metastatic parathyroid carcinoma. Despite undergoing treatment with bisphosphonates, cinacalcet hydrochloride, and forced diuresis, the patient`s condition deteriorated rapidly due to resistant hypercalcemia. Surgery performed because of spinal metastasis and forced diuresis lowered calcium levels, albeit they remained in the hypercalcemic range and significantly increased when forced diuresis was stopped. Considering a palliative situation to overcome hypercalcemia, we decided to administer denosumab, a monoclonal antibody that binds to the receptor activator of nuclear factor-kappa B ligand. After a single subcutaneous administration of 60 mg denosumab, calcium levels normalized within one day. Subsequent denosumab injections led to permanent control of serum calcium for more than 2 years despite rising parathyroid hormone levels and repeated surgeries. Together with recent cases in the literature supporting our observation, we believe that denosumab is relevant for future trials and represents an effective tool to control hypercalcemia in patients with advanced stages of parathyroid cancer. LEARNING POINTS: Severe hypercalcemia is the most common cause of death in patients with parathyroid carcinoma.The monoclonal antibody denosumab rapidly lowered severely elevated serum calcium levels due to parathyrotoxicosis.Denosumab was effective in the long-term treatment of hypercalcemia despite progression of parathyroid carcinoma.

Modified-release hydrocortisone decreases BMI and HbA1c in patients with primary and secondary adrenal insufficiency.

OBJECTIVE: Patients with adrenal insufficiency (AI) have impaired health-related quality of life (HRQoL), which is thought to be in part due to unphysiological glucocorticoid replacement therapy. The aim was to compare once-daily hydrocortisone (HC) dual-release tablet (modified-release) with conventional HC therapy regarding clinical data and HRQoL. DESIGN AND METHODS: We conducted an open, prospective trial at one endocrine center. There were 15 of 26 patients with primary AI, nine of 18 patients with secondary AI, and six congenital adrenal hyperplasia patients switched to modified-release HC therapy by their own decision. We evaluated clinical outcome and disease-specific HRQoL by using AddiQoL questionnaire at baseline and at follow-up (median 202 days (85-498)). RESULTS: Patients on modified-release HC (n=30) showed significant decreases in BMI (26.0±0.75-25.6±0.71, P for change=0.006) and HbA1c (6.04±0.29-5.86±0.28, P for change=0.005), whereas patients remaining on conventional HC (n=20) showed no change in these parameters (P for interaction=0.029 and 0.017 respectively). No significant change in AddiQoL score were found in the modified-release HC group (83.8 baseline and 84.9 at follow-up; P for change=0.629). In the conventional HC group, there was a significant decrease in scores (84.0 baseline and 80.9 at follow-up; P for change=0.016), with a between-treatment P for interaction of 0.066. The fatigue subscore of AddiQoL showed the same pattern with a significant decrease (P for change=0.024) in patients on conventional HC therapy (P for interaction=0.116). CONCLUSIONS: Modified-release HC decreases BMI and HbA1c compared with conventional HC treatment. In addition, it seems to stabilize HRQoL over time.

Sexual well-being in adult male patients with congenital adrenal hyperplasia.

Introduction. Men with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency show impaired fecundity due to testicular adrenal rest tumors and/or suppression of the gonadal axis. Sexual well-being might be an additional factor; however, no data exists. Patients and Methods. Prospective longitudinal monocentric study included 20 male CAH patients (14 salt wasting, 6 simple virilizing; age 18-49 yr). Clinical assessment, testicular ultrasound, biochemical and hormonal parameters, three validated self-assessment questionnaires (SF-36, GBB-24, and HADS), and male Brief Sexual Function Inventory (BSFI) were analyzed at baseline and after two years. Results. Basal LH and testosterone levels suggested normal testicular function. LH and FSH responses to GnRH were more pronounced in patients with a good therapy control according to androstenedione/testosterone ratio < 0.2. This group had significant higher percentage of patients on dexamethasone medication. GBB-24, HADS, and SF-36 showed impaired z-scores and no changes at follow-up. BSFI revealed impairments in dimensions "sexual drive," "erections," and "ejaculations," whereas "problem assessment" and "overall satisfaction" revealed normal z-scores. Androstenedione levels correlated (P = 0.036) inversely with z-scores for "sexual drive" with higher levels associated with impaired "sexual drive." Conclusion. Male CAH patients showed a partly impaired sexual well-being which might be an additional factor for reduced fecundity.

BclI polymorphism of the glucocorticoid receptor gene is associated with increased bone resorption in patients on glucocorticoid replacement therapy.

CONTEXT: Patients with primary adrenal insufficiency (PAI) and patients with congenital adrenal hyperplasia (CAH) receive weight-adapted standard glucocorticoid replacement therapy. Clinically, some patients appear more sensitive to therapeutic administration of glucocorticoids than others. Glucocorticoid sensitivity is at least partially genetically determined by polymorphisms of the glucocorticoid receptor (GR) and might influence bone mineral density (BMD). OBJECTIVES: To determine if bone turnover markers and BMD are associated with the GR gene polymorphism BclI in patients with PAI and CAH. DESIGN AND PATIENTS: A prospective, cross-sectional study including 74 PAI and 38 CAH patients. BMD was evaluated by DXA. Serum levels of bone turnover markers, minerals, vitamins and hormones, and urinary crosslinks were measured. RESULTS: Patients carrying the homozygous BclI polymorphism (GG) had significantly higher serum ß-CrossLaps (0.37 ± 0.34 µg/l; P < 0.05) and urinary collagen crosslinks (NTX, 68.1 ± 32.4 nmol/g; P < 0.005) despite receiving the lowest average daily hydrocortisone dose of 9.9 ± 3.7 mg/m(2) (P < 0.05). The GG genotype occurred significantly more frequently in patients with increased NTX (OR=6.7, 95% CI = 1.78-25.38) than in patients with normal NTX. However, BMD was not significantly different between different allelic variants. No significant differences in associations of the genotypes with outcomes (or in clinical characteristics) were found between the sexes. CONCLUSIONS: Although the sample sizes were relatively small and the results should be interpreted with caution, this study suggests that the homozygous (GG) genotype may be associated with higher bone resorption in adult PAI and CAH patients. GG-carriers needed a lower hydrocortisone dose on average supporting the concept that this GR variant is associated with increased cortisol sensitivity.

Improvement of health-related quality of life in adult women with 21-hydroxylase deficiency over a seven-year period.

Health related quality of life (HRQoL) is impaired in adult patients with 21-hydroxylase deficiency (21-OHD). Up to now, only cross-sectional and no longitudinal studies are available. It is not known if HRQoL can be improved in adult 21-OHD patients. We performed a longitudinal, prospective, single centre, follow-up study over seven years including 15 adult female 21-OHD patients. Two standardized questionnaires (Short Form 12 (SF-12); Hospital Anxiety and Depression Scale (HADS)) were completed in 2003, 2006 and 2010. Adjustment for age and sex was performed by transformation of score values into age- and sex-adjusted Z-scores using data sets from respective normative groups. Data regarding glucocorticoid therapy, clinical and hormonal parameters were assessed. We found that two of eight scales of SF-12 showed a significant improvement and four of eight scales a positive trend to better scores. No significant changes were seen in scores for HADS or for steroid hormone levels. Daily hydrocortisone equivalent dose per body surface significantly decreased over the study period. No changes in BMI were observed over the study period. We conclude that improvement of HRQoL in adult female 21-OHD patients is possible. Several factors might be involved in this improvement including reduced daily hydrocortisone equivalent dose per body surface.

Quality of life is less impaired in adults with congenital adrenal hyperplasia because of 21-hydroxylase deficiency than in patients with primary adrenal insufficiency.

OBJECTIVE: Current replacement regimens fail to restore well-being in patients with primary adrenal insufficiency (PAI). Data on health-related quality of life (HRQoL) in patients with congenital adrenal hyperplasia (CAH) are scarce, inconsistent and largely restricted to women. The objective of the study therefore was to study HRQoL in CAH because of 21-hydroxylase deficiency in comparison with PAI and healthy controls. DESIGN/PATIENTS: In a cross-sectional study, 81 German CAH patients from two tertiary care centres (45 women, 36 men; 71 classical, 10 nonclassical, age 18-65 years) completed three validated self-assessment questionnaires [Short Form-36 (SF-36), Giessen Subjective Complaints List (GBB-24), Hospital Anxiety and Depression Scale (HADS)]. Results were compared to sex- and age-matched controls from questionnaire-specific German reference cohorts and German PAI patients. RESULTS: Congenital adrenal hyperplasia patients had impaired HRQoL in three of five GBB-24 scores whereas SF-36 and HADS scores did not differ from controls. PAI patients showed impairment in more dimensions of the applied tests and, in women, significantly worse scores in several dimensions compared to CAH patients (physical functioning, vitality, social functioning, mental health dimensions of the SF-36, P<0·05 and HADS anxiety score, P<0·05). CONCLUSIONS: HRQoL in CAH is only mildly impaired and significantly less than in PAI patients. Differences between PAI and CAH in HRQoL suggest relevant modulating factors of HRQoL other than hormone replacement therapy itself.

Spinal cord atrophy in triple A syndrome associated with a novel compound heterozygous mutation.

A 38-year-old male patient was admitted with slowly progressive spastic gait disturbance. Imaging revealed general spinal cord atrophy. Because of adrenal insufficiency, alacrima and achalasia, triple A syndrome was suspected. This is a case report of a triple A syndrome patient with a predominance of neurological features and a new heterozygous compound mutation in triple A syndrome gene.

Delayed diagnosis of adrenal insufficiency is common: a cross-sectional study in 216 patients.

INTRODUCTION: Little information is available on patients with adrenal insufficiency (AI) in regard to complaints before diagnosis, time until correct diagnosis, false diagnosis, and professional changes due to the diagnosis. OBJECTIVE: We retrospectively evaluated circumstances before and at diagnosis of AI in patients with primary and secondary AI by using established Hospital Anxiety and Depression Scale, Short Form-36 and Giessen Complaint List (GBB-24) questionnaires, and a self-established general registration form. METHODS: In this cross-sectional study, questionnaire sets were available from 216 patients (primary AI, n = 99; secondary AI, n = 117). Time duration before treatment, underlying diagnoses, and disease symptoms were verified by questionnaires and review of medical records. Results regarding subjective health status (SHS) were compared with sex- and age-matched controls drawn from questionnaire-specific reference cohorts. RESULTS: Less than 30% of woman and 50% of men with AI were diagnosed within the first 6 months after onset of symptoms. Twenty percent of patients suffered >5 years before being diagnosed. More than 67% of patients consulted at least 3 physicians, and 68% were primarily false diagnosed. The most common false diagnoses were of psychiatric and gastrointestinal origin. Overall, patients with AI showed an impaired SHS compared with controls, and patients who were diagnosed correctly within 3 months showed a significantly better SHS. CONCLUSIONS: Because of the unspecific symptoms, diagnosis is often delayed, not recognized by physicians or diagnosed falsely. An early diagnosis is necessary and might positively influence SHS in patients with AI.

Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies.

OBJECTIVE: Adrenal crisis (AC) is a life-threatening complication of adrenal insufficiency (AI). Here, we evaluated frequency, causes and risk factors of AC in patients with chronic AI. METHODS: In a cross-sectional study, 883 patients with AI were contacted by mail. Five-hundred and twenty-six patients agreed to participate and received a disease-specific questionnaire. RESULTS: Four-hundred and forty-four datasets were available for analysis (primary AI (PAI), n=254; secondary AI (SAI), n=190). Forty-two percent (PAI 47% and SAI 35%) reported at least one crisis. Three hundred and eighty-four AC in 6092 patient years were documented (frequency of 6.3 crises/100 patient years). Precipitating causes were mainly gastrointestinal infection and fever (45%) but also other stressful events (e.g. major pain, surgery, psychic distress, heat and pregnancy). Sudden onset of apparently unexplained AC was also reported (PAI 6.6% and SAI 12.7%). Patients with PAI reported more frequent emergency glucocorticoid administration (42.5 vs 28.4%, P=0.003). Crisis incidence was not influenced by educational status, body mass index, glucocorticoid dose, DHEA treatment, age at diagnosis, hypogonadism, hypothyroidism or GH deficiency. In PAI, patients with concomitant non-endocrine disease were at higher risk of crisis (odds ratio (OR)=2.02, 95% confidence interval (CI) 1.05-3.89, P=0.036). In SAI, female sex (OR=2.18, 95% CI 1.06-4.5, P=0.035) and diabetes insipidus (OR=2.71, 95% CI 1.22-5.99, P=0.014) were associated with higher crisis incidence. CONCLUSION: AC occurs in a substantial proportion of patients with chronic AI, mainly triggered by infectious disease. Only a limited number of risk factors suitable for targeting prevention of AC were identified. These findings indicate the need for new concepts of crisis prevention in patients with AI.

Influence of hydrocortisone dosage scheme on health-related quality of life in patients with adrenal insufficiency.

CONTEXT: Recent studies suggest that current glucocorticoid replacement therapies fail to completely restore well-being in patients with adrenal insufficiency (AI). OBJECTIVE: The objective of this study was to investigate health-related quality of life (QoL) in patients with AI depending on dose and frequency of daily intake of hydrocortisone (HC). DESIGN AND PATIENTS: In a cross-sectional study, primary and secondary AI patients were contacted and asked to complete three validated self-assessment questionnaires [Short Form-36 (SF-36), Giessen Complaint List (GBB-24), Hospital Anxiety and Depression Scale (HADS)]. HC doses were corrected for body surface area. Results were compared with sex- and age-matched controls drawn from the questionnaire-specific reference cohort. RESULTS: Completed questionnaire sets were available from 334 patients on HC (primary AI n = 194; secondary AI n = 140). Patients on higher doses of HC (>30 mg/day) showed significantly impaired subjective health status in two of eight SF-36 dimensions, and three of five GBB-24 scales compared with those on lower HC doses. No significant differences in QoL were found between lower HC doses (15-30 mg/day) or between primary or secondary AI. Patients on HC with thrice daily intake showed significantly impaired QoL in one of eight SF-36 dimensions (15-20 mg/day, 20-25 mg/day), in one of five GBB-24 scales (15-20 mg/day), as well as higher anxiety scores. CONCLUSIONS: Health-related QoL was impaired in patients with primary and secondary AI. HC doses above 30 mg/day were associated with a worse health status. Thrice daily intake of HC was not superior to twice daily intake. Our data support the perception that current replacement strategies are still insufficient to fully restore well-being and daily performance.

Frequent incidental discovery of phaeochromocytoma: data from a German cohort of 201 phaeochromocytoma.

CONTEXT: Adrenal and extra-adrenal phaeochromocytoma are chromaffin cell-derived tumours that are discovered due to classical symptom triad with headache, sweating and palpitations combined with persistent or paroxysmal hypertension. However, an increasing proportion of phaeochromocytoma seems to be discovered incidentally upon abdominal imaging. OBJECTIVE: To specify the exact circumstances of discovery of adrenal and extra-adrenal phaeochromocytoma. DESIGN AND PATIENTS: Four German endocrine centres participated in this retrospective study. MEDICAL: records of 201 patients with adrenal and extra-adrenal phaeochromocytoma who were diagnosed between 1973 and 2007 were analyzed. RESULTS: The typical triad of symptoms was found only in 10% of cases. Ten percent of patients presented were without clinical symptoms and 6.1% were normotensive. Documented blood pressure peaks occurred in 44.1% of cases. In 24 patients (12.2%), phaeochromocytoma was malignant. Before 1985, <10% of cases were incidentally discovered, whereas thereafter the frequency was >25% (29.4% of the total study population). Patients with incidentally detected phaeochromocytoma were significantly older (53.1+/-1.9 vs 47.0+/-1.3 years; P<0.05) and often had less blood pressure peaks (37.0 vs 70.7%; P<0.001) than patients in whom the diagnosis was suspected on clinical grounds. Of phaeochromocytomas 94.4% were intra-adrenal tumours, of which 12.9% were bilateral. Bilateral tumours were significantly smaller than unilateral tumours (36.6+/-14.7 vs 52.5+/-34.3 mm; P<0.05), whereas extra-adrenal tumours had a mean diameter of 52.6+/-28.7 mm. CONCLUSIONS: Owing to better availability and accessibility of imaging procedures, the number of incidentally discovered phaeochromocytoma is increasing and reaches nearly 30% in our study population. Every adrenal incidentaloma should be investigated for the presence of phaeochromocytoma.

Impaired subjective health status in chronic adrenal insufficiency: impact of different glucocorticoid replacement regimens.

CONTEXT: Recent studies have suggested that current glucocorticoid replacement therapies fail to fully restore well-being in patients with adrenal insufficiency (AI). OBJECTIVE: To investigate the effect of different glucocorticoid preparations used for replacement therapy on subjective health status (SHS) in AI. DESIGN AND PATIENTS: In a cross-sectional study, primary and secondary AI patients were contacted by mail. Individual glucocorticoid replacement regimens, underlying diagnoses and comorbidities were verified by questionnaires and review of medical records. Patients were asked to complete three validated self-assessment questionnaires (Short Form 36 (SF-36), Giessen Complaint List (GBB-24), and Hospital Anxiety and Depression Scale). Results were compared with sex- and age-matched controls drawn from the questionnaire-specific reference cohort. RESULTS: Of the 883 patients identified, 526 agreed to participate in the study. Completed questionnaire sets were available from 427 patients (primary AI n=232; secondary AI n=195). AI patients showed significantly impaired SHS compared with controls irrespective of the glucocorticoid used for replacement. The only difference in SHS between patients on prednisolone (PR) and hydrocortisone (all patients and sub-analysis for primary AI) was significant higher bodily pain (lower Z-score in SF-36) in patients on PR (P<0.05, P<0.01 respectively). In patients with secondary AI, the PR group showed significantly (P<0.05) less heart complaints (lower Z-score) in the GBB questionnaire compared with the cortisone acetate group. CONCLUSIONS: Glucocorticoid replacement therapy with PR seems to be equivalent to hydrocortisone regarding SHS in patients with AI. However, SHS remains impaired in all patient groups suggesting a need for further improved glucocorticoid replacement strategies.

Cushing's syndrome due to ACTH-secreting pheochromocytoma.

Ectopic secretion of adrenocorticotropic hormone (ACTH) is an infrequent cause of Cushing's syndrome. We report a case of ectopic ACTH syndrome caused by a pheochromocytoma. A 53-year-old female with clinical features of Cushing s syndrome presented with serious recurrent hypertensive crisis. Endocrinological investigation confirmed the diagnosis of ectopic ACTH production and revealed markedly elevated urinary catecholamines leading to the diagnosis of pheochromocytoma. Abdominal computerized tomography (CT) scan showed a 3.5 cm left adrenal mass and a nodular hypertrophic right adrenal gland. Bilateral selective adrenal vein catheterization suggested bilateral pheochromocytoma. After treatment with phenoxybenzamine, bilateral adrenalectomy was performed and resulted in remission of Cushing's syndrome and hypertensive crisis. In addition, this article provides a short guideline for endocrine testing if Cushing's disease or pheochromocytoma is suspected. However, the most important message of this article is to think of them.

[Long-term follow-up of patients with suprasellar germinomas]. / Langzeitverlauf bei Patienten mit suprasellären Germinomen.

BACKGROUND: Suprasellar germinomas are rare intracranial neoplasms, which mainly occur in children and adolescents and manifest with endocrine symptoms and/or compression syndromes. PATIENTS AND METHODS: The clinical, hormonal and morphological findings as well as treatment and complications were investigated in seven patients (six male, one female) with germinomas. RESULTS: Mean age at diagnosis was 19.7 years (range 15-32 years). First disease-related symptoms were diabetes insipidus (three patients), loss of libido (two patients), pseudopubertas praecox (one patient), and dwarfism (one patient). However, decisive symptoms leading to final diagnosis were visual disturbances (five patients), pubertas tarda (one patient), and hypogonadism (one patient). All patients were treated by transcranial radiation with a dose of 40-54 Gy. One patient received additional chemotherapy with cisplatin, etoposide, and ifosfamide (PEI). Patients were followed up for 14.6 years (range 7-27 years). Intracranial and pulmonary relapses were observed in two patients. Panhypopituitarism and diabetes insipidus were seen in all patients after treatment. Two patients suffered from loss of vision, two further patients from unilateral amaurosis. One patient developed epilepsy and persistent cognitive impairment. Long-term follow-up shows that two patients died from recurrent disease and decompensated liver cirrhosis, respectively. The other patients are long-term survivors. Full social integration with employment was possible in one case. CONCLUSION: Suprasellar germinomas cause endocrine symptoms during early tumor stages, however, diagnosis is generally established when ocular symptoms related to tumor compression are already present. Long-term survival is characterized by panhypopituitarism, diabetes insipidus and, partly, ocular or cerebral defects.

Long-term management in five cases of TSH-secreting pituitary adenomas: a single center study and review of the literature.

OBJECTIVE: TSH-secreting pituitary tumors (TSH-omas) are a rare cause of hyperthyroidism and account for <1% of all pituitary adenomas. Failure to recognize the presence of a TSH-oma may result in dramatic consequences such as thyroid ablation that may cause further growth in pituitary tumor. The primary goal of the treatment of TSH-omas is to remove the pituitary tumor. Medical treatment includes dopaminergic agonists or somatostatin analogs. METHODS AND RESULTS: We report five cases of TSH-oma diagnosed between 1997 and 2006 and review the literature. All the patients are females with an age range from 54 to 65 years at diagnosis. Four of the five patients had at least one event of thyroid surgery due to goiter or nodule of unknown dignity. Three of the five patients had a stroke before the diagnosis of TSH-oma, probably due to hypertension, or smoking and contraceptive treatment. One patient with invasive tumor growth received stereotactic radiotherapy (and developed panhypopituitarism after operation), another patient received somatostatin analogs preoperatively and successfully underwent transsphenoidal operation. Three of the five patients received dopaminergic agonists (bromocriptine 5 mg daily or cabergoline 0.5-0.75 mg per week), because they refused surgical therapy or the tumor was stable under dopaminergic therapy. All patients have been followed-up for 2.5-8 years. A normalization of circulating thyroid hormone levels was achieved in all patients. The patient who underwent operation shows no recurrence of the disease. The other patients have a stable pituitary mass without signs of growth. CONCLUSION: We report the successful long-term treatment of TSH-omas with different therapies.