HORMONE SUBSTITUTION AFTER GASTRIC BYPASS SURGERY IN PATIENTS WITH HYPOPITUITARISM SECONDARY TO CRANIOPHARYNGIOMA.

OBJECTIVE: Craniopharyngiomas (CPs) are benign brain tumors presenting frequently in childhood and are treated by surgery with or without radiotherapy. About 50% of cured patients suffer from eating disorders and obesity due to hypothalamic damage, as well as hypopituitarism, necessitating subsequent hormone substitution therapy. Gastric bypass surgery has been reported to be an efficient treatment strategy for morbid hypothalamic obesity. However, so far it is unknown whether oral hormone substitution is affected by impaired intestinal drug absorption, potentially leading to severe hypopituitarism or pituitary crisis. METHODS: Four morbidly obese CP patients with panhypopituitarism treated by gastric bypass surgery were included in this retrospective analysis. Dosages of hormone substitution therapy, blood concentrations of hormones, potential complications of impaired drug absorption, and anthropometric characteristics were investigated pre- and postoperatively after 6 to 14 months and 13 to 65 months. RESULTS: In all CP patients (3 female/1 male; baseline body mass index, 49 ± 7 kg/m(2)), gastric bypass resulted in distinct weight loss (-35 ± 27 kg). In follow-up examinations, mean daily dosage of thyroid hormone (levothyroxinebaseline 156 ± 44 µg/day versus levothyroxinefollow-up 150 ± 30 µg/day), hydrocortisone (hydrocortisonebaseline 29 ± 12 mg/day versus hydrocortisonefollow-up 26 ± 2 mg/day), growth-hormone (somatotropinbaseline 0.9 ± 0.5 mg/day versus somatotropinfollow-up 1.0 ± 0.4 mg/day), and desmopressin (desmopressinbaseline 222 ± 96 µg/day versus desmopressinfollow-up 222 ± 96 µg/day) substitution was unchanged. No patient developed adrenal insufficiency. Oral thyroid/hydrocortisone absorption testing performed in 1 patient indicated sufficient gastrointestinal drug absorption after bariatric surgery. CONCLUSION: Our preliminary results suggest that oral hormone substitution therapy is not impaired following gastric bypass operation in CP patients with morbid obesity, indicating that it might be a safe and effective treatment strategy.

Measurements of Plasma-Free Metanephrines by Immunoassay Versus Urinary Metanephrines and Catecholamines by Liquid Chromatography with Amperometric Detection for the Diagnosis of Pheochromocytoma/Paraganglioma.

Studies conflict concerning the use of enzyme immunoassays (EIA) for plasma free metanephrines (P-MNs) vs. other methods for pheochromocytoma/paraganglioma (PPGL) diagnosis. We compared commercially available EIAs for P-MNs with high-pressure liquid chromatography (HPLC) for 24 h-urinary MNs (U-MNs) and -catecholamines (U-CATs). 943 (565 female, 378 male) patients (54 PPGL, 889 Non-PPGL) were studied. Simultaneous measurements of all parameters analyzed at the central lab of our university hospital was mandatory for inclusion. Sensitivity of P-MNs (94.4%) was similar to that of U-MNs (100%), and both were higher than of U-CATs (77.8%), specificity of P-MNs (100%) higher than of U-MNs (73.6%), and similar to U-CATs (99.8%). With the recently proposed downward adjusted ULN of P-MNs to correct for the reported negative bias of the EIAs sensitivity (98.1%) raised non-significantly, but specificity decreased significantly (94.8%). Areas under receiver-operating characteristic curves indicated comparable diagnostic performance of P-MNs (0.989) vs. U-MNs (0.995), both better than U-CATs (0.956). In summary, the EIAs to measure P-MNs performed similarly to U-MNs by HPLC, and both better than U-CATs by HPLC. The post-test probability of PPGL given a positive test result was best for P-MNs, and higher than for the other pairs of analytes. Downward corrections of ULN of P-MNs did not improve test performances.

Positive central lymph-nodes are underdiagnosed in patients with Bethesda V cytology in an endemic goiter region.

BACKGROUND: Fine needle aspiration (FNA) is a significant diagnostic procedure for detecting malignancy in patients with nodular thyroid disease. A high proportion of patients with cytological diagnosed follicular neoplasia (Bethesda IV and V) ultimately have thyroid cancer. The aim of this study was to evaluate the incidence of preoperatively undiagnosed central lymph node metastasis in patients with multinodular goiter (MNG). METHODS: Patients who underwent FNA and were classified as Bethesda IV/V were included. Applying a radical approach, all patients underwent (hemi)thyroidectomy and prophylactic unilateral central neck dissection. RESULTS: During our study period 2009-2013, 60 patients (19.7%) were classified as Bethesda IV and 21 (6.9%) Bethesda V. Final histopathological results revealed malignancy in 35 (43.2%) of 81 Bethesda IV/V nodules. Of the nodules classified as Bethesda IV, 20 (33.3%) showed malignancy in the final histology. Ten patients (16.7%) had papillary micro-carcinoma (mPTC, <10 mm), 4 (6.6%) PTC and 6 (10%) follicular thyroid cancer. Fifteen of 21 (71.4%) Bethesda V nodules were revealed as PTC of whom seven (33.3%) patients also had lymph-node metastases. CONCLUSIONS: While 33.3% of the patients with PTC, preoperatively classified as Bethesda V, had previously undetected positive lymph-nodes, only one patient with Bethesda IV had lymph-node metastasis.

Increased ATP synthesis might counteract hepatic lipid accumulation in acromegaly.

Patients with active acromegaly (ACRO) exhibit low hepatocellular lipids (HCL), despite pronounced insulin resistance (IR). This contrasts the strong association of IR with nonalcoholic fatty liver disease in the general population. Since low HCL levels in ACRO might be caused by changes in oxidative substrate metabolism, we investigated mitochondrial activity and plasma metabolomics/lipidomics in active ACRO. Fifteen subjects with ACRO and seventeen healthy controls, matched for age, BMI, sex, and body composition, underwent 31P/1H-7-T MR spectroscopy of the liver and skeletal muscle as well as plasma metabolomic profiling and an oral glucose tolerance test. Subjects with ACRO showed significantly lower HCL levels, but the ATP synthesis rate was significantly increased compared with that in controls. Furthermore, a decreased ratio of unsaturated-to-saturated intrahepatocellular fatty acids was found in subjects with ACRO. Within assessed plasma lipids, lipidomics, and metabolomics, decreased carnitine species also indicated increased mitochondrial activity. We therefore concluded that excess of growth hormone (GH) in humans counteracts HCL accumulation by increased hepatic ATP synthesis. This was accompanied by a decreased ratio of unsaturated-to-saturated lipids in hepatocytes and by a metabolomic profile, reflecting the increase in mitochondrial activity. Thus, these findings help to better understanding of GH-regulated antisteatotic pathways and provide a better insight into potentially novel therapeutic targets for treating NAFLD.

Thyroid ultrasound versus antithyroid peroxidase antibody determination: a cohort study of four hundred fifty-one subjects.

Autoimmune thyroiditis is mirrored by a hypoechoic ultrasound pattern. We determined diagnostic precision of thyroid sonography compared to that of anti-thyroid peroxidase antibody (TPOAb) concentration. Ambulatory patients with unknown thyroid status (n = 451; 407 female, ages 44 +/- 16 years; 45 male, ages 50 +/- 14 years) excluding those with suspected hyperthyroidism or on drugs known to cause hypothyroidism were recruited consecutively. Subjects were recruited from a specialized thyroid outpatient unit with higher frequencies of thyroid disorders than in the general population. Before determination of thyroid function and TPOAb concentration thyroid volume (normal values: women < 12 mL, men < 14 mL) and echogenicity (grade 1 = normal: similar to submandibular gland, hyperechoic to neck muscles; grade 2: hypoechoic to submandibular gland, hyperechoic to neck muscles, grade 3: iso-/hypoechoic to neck muscles) were determined. Positive predictive value of grade 3 pattern for detection of autoimmune thyroiditis was 94% (with overt hypothyroidism) and 96% (with any degree of hypothyroidism), that of grade 2 or 3 85% and 87%, respectively. Negative predictive value of grade 1 pattern for detection of euthyroid TPOAb negative subjects was 91%. Goiter was present in 31% and 21% of TPOAb postive and negative subjects, respectively, while 11% and 15% had an atrophic thyroid gland (p = not significant [n.s.]). Given a high intraobserver and interobserver agreement abnormal thyroid ultrasound patterns were highly indicative of autoimmune thyroiditis and allowed the detection of thyroid dysfunction with 96% probability.

No evidence of ectopic lipid accumulation in the pathophysiology of the acromegalic cardiomyopathy.

CONTEXT: PATIENTS with acromegaly frequently display disturbances of glucose and lipid metabolism, which might contribute to their increased cardiovascular risk. Because insulin resistance and increased lipolysis have been linked to ectopic lipid deposition, altered lipid accumulation in the liver and the myocardium might contribute to metabolic and cardiac complications in these patients. OBJECTIVE: The aim of this study was to investigate myocardial (MYCL) and hepatic lipid content (HCL), insulin sensitivity, and cardiac function in active acromegaly and after control of GH excess through transsphenoidal surgery. PATIENTS: Ten patients with newly diagnosed acromegaly (ACRO_active) were compared with 12 healthy controls (CON), matched for age, body mass index, and gender. In seven patients GH excess was controlled, and they were compared with their active state. METHODS: MYCL and HCL were assessed by (1)H-magnetic resonance spectroscopy, pericardial fat and cardiac function by (1)H-magnetic resonance imaging, and insulin sensitivity and secretion by an oral glucose tolerance test. RESULTS: Although MYCL tended to be lower, HCL was significantly lower in ACRO_active compared with CON (HCL: 1.2% ± 1.2% vs 4.3% ± 3.5% of (1)H-magnetic resonance spectroscopy signal, P < .02). Parameters of systolic function and hypertrophy were significantly increased in ACRO_active compared with CON, as were insulin secretion and resistance. After the control of GH excess, HCL and MYCL remained unchanged, but pericardial fat was increased in the patients in whom GH excess was controlled (from 11.6 ± 5.5 to 14.7 ± 6.2 cm(2), P = .02). CONCLUSION: Acromegaly represents a unique condition characterized by low myocardial and hepatic lipid content despite decreased insulin sensitivity, hyperinsulinemia, and hyperglycemia. Hence, ectopic lipid accumulation does not appear to contribute to cardiac morbidity, and increased lipid oxidation might counteract ectopic lipid accumulation in GH excess.

Higher frequency of thyroid tumors in the right lobe.

Recently, using ultrasonography, we observed that the right lobe usually is larger compared with the left thyroid lobe. Since the higher cell number in a larger right lobe may confer a higher tumor risk, we investigated the location of benign and malignant lesions to test the hypothesis of a more frequent occurrence in this lobe. In 1,001 consecutive patients with benign thyroid lesions, tumors more frequently occurred in the right lobe (+21.5%, p = 0.0022). Furthermore, in 1,277 thyroid cancer patients with 1,302 thyroid cancers, the right lobe more often harbored the tumor initially (+22.9%, p = 0.0009). Our data show a larger proportion of both benign and malignant tumors in the right thyroid lobe.

Hyperprolactinaemia in hypothyroidism: clinical significance and impact of TSH normalization.

OBJECTIVES: Menstrual irregularities in hypothyroidism have been reported to occur less frequently than previously described. We therefore studied the influence of serum PRL in patients with newly diagnosed subclinical and overt hypothyroidism and in hyperprolactinaemic patients treated with T4 to distinguish the impact of hypothyroidism from that of confounding drugs on hyperprolactinaemia and menstrual irregularities. PATIENTS AND METHODS: PRL was determined in 1003 consecutive hypothyroid patients (TSH > 4.0 mU/l) at referral, and after TSH normalization in 84 (8%) initially hyperprolactinaemic (female, > 480 mU/l; male, > 432 mU/l) subjects. Medical history (psychotropic drugs and oestrogens) and menstrual patterns were assessed at referral and after 8 +/- 5 (mean +/- SD) months of T4 therapy. Pituitary magnetic resonance imaging (MRI) was offered to patients with persistently elevated PRL. RESULTS: Menstrual disturbancies (oligomenorrhoea/secondary amenorrhoea, O/A) were not more common (P = NS) in hyper- than in normoprolactinaemic women (26% and 16%, respectively). We observed no galactorrhoea and no correlation between PRL and TSH or O/A except in pregnant or lactating women (N = 11). Oestrogens or antidepressants (including selective serotonin reuptake inhibitors) did not cause hyperprolactinaemia but antipsychotic drugs did. PRL decreased with T4 therapy (P < 0.01) in patients not using confounding drugs (from 720 +/- 288 to 360 +/- 192 mU/l) but menstrual irregularities persisted. PRL remained unchanged in patients receiving antipsychotic treatment. PRL was also unchanged in patients with pituitary abnormalities (seven micro-, one macroadenoma). CONCLUSIONS: Hyperprolactinaemia was not an important feature in patients with newly diagnosed hypothyroidism. Neuroleptic drugs may cause persisting hyperprolactinaemia after TSH normalization. In addition, menstrual disturbancies do not relate to hyperprolactinaemia in hypothyroidism.