Thyroid Related Quality of Life in Elderly with Subclinical Hypothyroidism and Improvement on Levothyroxine is Distinct from that in Young Patients (TSAGE).

The aim of this study was to investigate in a longitudinal approach whether levothyroxine (LT4) substitution has a different impact on quality of life (QoL) and thyroid related QoL in younger (<40 years) and older subjects (>60 years) with elevated thyroid-stimulating hormone (TSH) concentrations. The study included male and female patients with newly diagnosed, untreated subclinical hypothyroidism defined by TSH>8 mU/l. Patients were recruited throughout Germany from 2013-2016 and evaluated by clinical assessment, blood sampling and questionnaires for health related QoL and thyroid-disease thyroid-related QoL (ThyPRO) at time of diagnosis and six months after initiation of LT4 treatment. We found significantly lower QoL in both young and old patients with subclinical hypothyroidism compared to age-matched healthy individuals. Higher scores on follow-up were found in all patients irrespective of age, indicating better QoL on LT4 therapy. Analysis of the ThyPRO questionnaire showed that old patients experienced less Emotional Susceptibility, Tiredness, and Impaired Day Life on LT4, while young patients reported less Cognitive Complaints, Emotional Susceptibility, and Impaired Day Life compared to baseline assessment. Hypothyroidism with TSH concentrations>8 mU/l is associated with impairment in general and ThyPRO QoL in young and old age. Older patients benefited from LT4 therapy and remarkably show similar degree of improvement as younger patients, albeit with some thematic variation in ThyPRO QoL. Our data confirm current recommendations on initiation of LT4 substitution and suggest that this should not be withheld in elderly with TSH concentration above 8-10 mU/l.

[Iodinated contrast medium in patients with thyroid disorders]. / Jodhaltige Kontrastmittel bei Patienten mit Schilddrüsenerkrankungen.

BACKGROUND: Adequate intake of iodine is essential for normal thyroid function. However, sudden exposure to high amounts of iodine may cause thyroid dysfunction. AIM: The aims of this paper are to summarize the literature on the effects of iodinated contrast medium (CM) on thyroid function, the risk to develop CM-induced hyper- and hypothyroidism, and to describe procedures for clinical practice regarding diagnosis, prevention, and treatment of CM-induced hyperthyroidism. RESULTS: The occurrence of CM-induced hyperthyroidism is very rare (<0.5%). In Germany, thyroid function is commonly assessed with laboratory tests (TSH determination) before the use of iodinated CM. Older patients (>60 years) with autonomous thyroid and concomitant cardiac diseases are at particular risk of developing hyperthyroidism. The main focus of prevention is to identify patients at risk of developing iodine-induced hyperthyroidism and carry out further thyroid diagnostic procedures prior to CM use. In these patients, prophylaxis with perchlorate and/or thionamides is recommended or alternatively careful monitoring of the patients after use of CM. In patients with overt hyperthyroidism, the use of CM is contraindicated. Iodine-induced hypothyroidism is predominantly found in regions with sufficient iodine supply and in patients with autoimmune thyroiditis. Free iodide influences iodide uptake into the thyroid and therefore interferes with nuclear diagnostic procedures like thyroid scintigraphy as well as radioactive iodine treatment which may be hampered for 2 months or longer after use of CM.

Prevalence and determinants of osteoporosis in patients with type 1 and type 2 diabetes mellitus.

BACKGROUND: Increased risk of osteoporosis and its clinical significance in patients with diabetes is controversial. We analyze osteoporosis prevalence and determinants of bone mineral density (BMD) in patients with type 1 and 2 diabetes. METHODS: Three hundred and ninety-eight consecutive diabetic patients from a single outpatient clinic received a standardized questionnaire on osteoporosis risk factors, and were evaluated for diabetes-related complications, HbA1c levels, and lumbar spine (LS) and femoral neck (FN) BMD. Of these, 139 (71 men, 68 women) type 1 and 243 (115 men, 128 women) type 2 diabetes patients were included in the study. BMD (T-scores and values adjusted for age, BMI and duration of disease) was compared between patient groups and between patients with type 2 diabetes and population-based controls (255 men, 249 women). RESULTS: For both genders, adjusted BMD was not different between the type 1 and type 2 diabetes groups but was higher in the type 2 group compared with controls (p < 0.0001). Osteoporosis prevalence (BMD T-score < -2.5 SD) at FN and LS was equivalent in the type 1 and type 2 diabetes groups, but lower in type 2 patients compared with controls (FN: 13.0% vs 21.2%, LS: 6.1% vs 14.9% men; FN: 21.9% vs 32.1%, LS: 9.4% vs 26.9% women). Osteoporosis prevalence was higher at FN-BMD than at LS-BMD. BMD was positively correlated with BMI and negatively correlated with age, but not correlated with diabetes-specific parameters (therapy, HbBA1c, micro- and macrovascular complications) in all subgroups. Fragility fracture prevalence was low (5.2%) and not different between diabetes groups. Fracture patients had lower BMDs compared with those without fractures; however, BMD T-score was above -2.5 SD in most patients. CONCLUSIONS: Diabetes-specific parameters did not predict BMD. Fracture occurrence was similar in both diabetes groups and related to lower BMD, but seems unrelated to the threshold T-score, <-2.5 SD. These results suggest that osteoporosis, and related fractures, is a clinically significant and commonly underestimated problem in diabetes patients.

Evaluation of thyroid nodules--combined use of (99m)Tc-methylisobutylnitrile scintigraphy and aspiration cytology to assess risk of malignancy and stratify patients for surgical or nonsurgical therapy--a retrospective cohort study.

OBJECTIVE: Thyroid nodules are a common clinical problem, and differentiation between benign and malignant nodules is essential. The aim of this study was to evaluate an approach for cold thyroid nodules including (99m)Tc-methylisobutylnitrile (MIBI) scintigraphy to assess risk of malignancy and stratify patients for therapy. DESIGN: Retrospective cohort study; 391 patients with at least one cold thyroid nodule were consecutively admitted (between 1 January 2004 and 31 December 2006) and recommended for surgical or nonsurgical therapy. MEASUREMENTS: Thyroid ultrasonography, (99m)Tc-pertechnetate scintigraphy, laboratory tests, fine needle aspiration cytology (FNAC) and MIBI scintigraphy. RESULTS: 57·3% (224/391) had one cold nodule, 17·9% (70/391) had several cold nodules, and 24·8% (97/391) had both cold and hot nodules. MIBI scintigraphy was classified into 'positive' (16·1%, 63/391), 'weakly positive' (19·2%, 75/391) or 'negative' (64·7%, 253/391). FNAC was classified into benign (87·9%, 247/281), nondiagnostic (6·8%, 19/281) or suspicious/malignant (5·3%, 15/281). 127 patients received surgery, revealing malignancy in 13·3% (17/127), predominantly papillary (64·7%, 11/17) and follicular carcinoma (23·5%, 4/17). MIBI scintigraphy was 'positive' (64·7%, 11/17) or 'weakly positive' (23·5%, 4/17) in most patients with malignant findings. FNAC was unavailable in 23·5% (4/17) with malignancy, positive in 38·5% (5/13) and negative in 61·5% (8/13). Among patients undergoing surgery, sensitivity, specificity, negative and positive predictive values for MIBI scintigraphy were 88·2%, 35·5%, 95·1% and 17·4%, for FNAC 38·5%, 90·6%, 90·6% and 38·5%, respectively, and for the combination (MIBI scan + FNAC) 92·3%, 30·6%, 96·3% and 16·9%. Benign MIBI-positive nodules were predominantly follicular adenomas (68%, 33/48). CONCLUSION: Evaluation of cold thyroid nodules by MIBI scintigraphy aids therapeutic decisions: MIBI-negative findings support nonsurgical management in about two-thirds of patients, while MIBI-positive findings have an increased risk of malignancy, supporting surgical therapy. However, the positive predictive value was low, which requires further research.

Inactivating calcium-sensing receptor mutations in patients with primary hyperparathyroidism.

OBJECTIVE: Primary hyperparathyroidism (HPT) is characterised by autonomous secretion of PTH from enlarged parathyroid glands leading, in most patients, to asymptomatic hypercalcaemia. Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant disorder caused by inactivating mutations in the calcium-sensing receptor (CaSR) gene; it is characterised by lifelong and usually asymptomatic hypercalcaemia. Establishing the correct diagnosis is important because surgery can be curative in HPT, but ineffective in FHH. There is overlap in the diagnostic criteria for the two disorders and some patients carrying inactivating mutations in the CaSR gene, which is suggestive of FHH, also have HPT with hyperplastic parathyroid glands or adenomas. DESIGN AND PATIENTS CaSR gene mutations were analysed and clinical and biochemical parameters evaluated in 139 consecutive outpatients presenting with hypercalcaemia and suspected of having HPT. RESULTS: Six different mutations of the CaSR gene were found in eight patients. In four patients, classical FHH was suspected based on clinical and biochemical results and was confirmed by the CaSR mutations. In the other four patients, HPT was diagnosed based on the biochemical profile or symptoms; in these four patients, the parathyroids were operated on and single adenomas were histologically confirmed. In all four patients, serum calcium decreased postoperatively; and in three patients, serum calcium normalised postoperatively. The CaSR mutations in these patients were R25X, E250K and Q926R. CONCLUSION: The coexistence of HPT and FHH in four of 139 patients suggests a pathogenetic role of CaSR mutations in HPT. Despite also having a CaSR mutation, these patients benefited from parathyroid surgery.

Elevated plasma endothelin-1 levels in diabetes mellitus.

BACKGROUND: This study compares plasma endothelin-1 (ET-1) levels in patients with diabetes mellitus or hypertension with healthy controls, and investigates whether ET-1 levels are correlated with glycemic control, metabolic parameters, and vascular complications. METHODS: The study population consisted of 103 patients with type 1 diabetes, 124 patients with type 2 diabetes, 35 hypertensive patients without diabetes mellitus, and 99 controls. RESULTS: Plasma ET-1 concentrations were significantly higher in patients with type 1 diabetes (0.28 +/- 0.34 fmol/mL, P =.001), type 2 diabetes (0.31 +/- 0.32 fmol/mL, P <.0001), and hypertension (0.35 +/- 0.26 fmol/mL, P <.0001) compared to controls (0.08 +/- 0.13 fmol/mL). Diabetic patients taking angiotensin converting enzyme (ACE) inhibitors had significantly lower plasma ET-1 levels than patients without (0.22 +/- 0.20 fmol/mL v 0.38 +/- 0.39 fmol/mL, P =.029). There were significant associations between ET-1 levels and age (r = 0.38, P <.05) and systolic blood pressure (BP) (r = 0.27, P <.05) in healthy controls. In diabetes we found only nonsignificant associations between ET-1 levels and age or vascular complications and a weak association between plasma ET-1 levels and glycemic control. CONCLUSIONS: Patients with diabetes or hypertension have elevated ET-1 levels, but do not exhibit positive correlations between ET-1 levels and BP, which was observed in healthy controls. Increased ET-1 levels do not induce hypertension in diabetes, but were lower in diabetic patients taking ACE inhibitors compared to those without ACE inhibitors. There is no significant association between ET-1 levels and vascular complications. These findings suggest that the plasma ET-1 level is not a marker of endothelial dysfunction but changes in plasma ET-1 levels may precede vascular complications associated with hypertension and diabetes.

Prevalence and clinical spectrum of nonsecretory medullary thyroid carcinoma in a series of 839 patients with sporadic medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) is characterized by the synthesis and secretion of calcitonin (Ct). MTC without Ct secretion has been reported on rare occasions. The aim of this study was to analyze the prevalence and clinical spectrum of nonsecretory MTC in two tertiary centers that cared for 839 patients with sporadic MTC. METHODS: Clinical, biochemical, histological, and immunohistological findings, and somatic RET mutations were analyzed, and long-term follow-up was documented. RESULTS: Seven patients with nonsecretory MTC were identified among 839 patients with sporadic MTC; thus, the prevalence rate of nonsecretory MTC was 0.83%. In these seven patients, Ct and carcinoembryonic antigen (CEA) levels were normal when MTC was initially diagnosed in the patients, despite advanced tumor stage. Ct and CEA levels remained undetectable in four patients; recurrence was indicated in one patient after 10 years of follow-up by routine anatomic imaging and increased CEA levels, and Ct levels became slightly elevated during follow-up, despite massive tumor load, in the remaining two patients. The diagnosis of MTC was confirmed by positive immunohistochemistry for Ct, CEA, and chromogranin A. A high Ki67 proliferation index (PI) (three patients) and a high proportion of RET 918-mutated cells (four patients), as well as poorly differentiated histology, were associated with aggressive biological behavior of the MTC. The prognosis for nonsecretory MTC varied between long-term survival (12.5 years) and rapid progression leading to death within 1.75 years after diagnosis. CONCLUSIONS: The prevalence of nonsecretory MTC was low (0.83% of patients with MTC). Diagnosis was often made at a clinically advanced tumor stage. The histological and immunohistological characteristics and the clinical course and prognosis of nonsecretory MTC are markedly heterogeneous. A high Ki-67 PI and a large proportion of cells with RET 918 mutations are associated with a poor prognosis.