Current landscape and support for practical initiation of oncological prehabilitation translatable to thyroid cancer: A position paper.

Despite a growing body of evidence for the effectiveness of prehabilitation, the uptake of prehabilitation in Europe remains low. Contributing factors range from limited awareness and understanding of prehabilitation to a lack of supporting infrastructure and reimbursement challenges. In this position paper, the authors propose a new comprehensive definition of prehabilitation and identify differentiated thyroid cancer as a type of cancer particularly well-suited for prehabilitation. To support clinicians with the implementation of prehabilitation programs in their clinics, the authors discuss the following practical solutions: a) find the most appropriate prehabilitation program for each patient; b) raise awareness among peers; c) develop evidence to demonstrate the effectiveness of prehabilitation; d) expand the interdisciplinary team; e) expand your network and make use of existing assets; f) utilize learnings from the COVID-19 pandemic.

Reliability of a computer-aided system in the evaluation of indeterminate ultrasound images of thyroid nodules.

Introduction: Computer-aided diagnostic (CAD) programs for malignancy risk stratification from ultrasound (US) imaging of thyroid nodules are being validated both experimentally and in real-world practice. However, they have not been tested for reliability in analyzing difficult or unclear images. Methods: US images with indeterminate characteristics were evaluated by five observers with different experience in US examination and by a commercial CAD program. The nodules, on which the observers widely agreed, were considered concordant and, if there was little agreement, not concordant or difficult to assess. The diagnostic performance of the readers and the CAD program was calculated and compared in both groups of nodule images. Results: In the group of concordant thyroid nodules (n = 37), the clinicians and the CAD system obtained similar levels of accuracy (77.0% vs 74.2%, respectively; P = 0.7) and no differences were found in sensitivity (SEN) (95.0% vs 87.5%, P = 0.2), specificity (SPE) (45.5 vs 49.4, respectively; P = 0.7), positive predictive value (PPV) (75.2% vs 77.7%, respectively; P = 0.8), nor negative predictive value (NPV) (85.6 vs 77.7, respectively; P = 0.3). When analyzing the non-concordant nodules (n = 43), the CAD system presented a decrease in accuracy of 4.2%, which was significantly lower than that observed by the experts (19.9%, P = 0.02). Conclusions: Clinical observers are similar to the CAD system in the US assessment of the risk of thyroid nodules. However, the AI system for thyroid nodules AmCAD-UT® showed more reliability in the analysis of unclear or misleading images.

Serum autoimmune gastritis markers, pepsinogen I and parietal cell antibodies, in patients with type 1 diabetes mellitus: a 5-year prospective study.

BACKGROUND AND AIM: To determine the temporal evolution of serum markers of autoimmune gastritis, mainly pepsinogen I (PI) and parietal cell antibodies (PCA), in patients with Type 1 diabetes mellitus (DM1). MATERIALS AND METHODS: A 5-yr prospective follow-up study of 168 DM1 patients (87 men, aged 31 ± 9.3 yr) attending the endocrinology outpatient clinic of a university hospital evaluated in 2001 and 2006. Serum PI, gastrin, hemoglobin, cobalamin concentrations, PCA and antibodies to intrinsic factor were measured. RESULTS: In 2001, 11 patients had low PI concentrations and positive PCA (group I), 11 had only low PI concentrations (group II), and 33 had only positive PCA (group III). After 5 yr, PI remained low and PCA positive in all patients from group I. In group II, PI remained low in 4 and normalized in 7. In group III, 4 patients presented low PI concentrations after 5 yr, which remained normal in the other 29 subjects. PCA became negative in 17 patients from group III. In 2001, 3 of the 11 patients of group I had low cobalamin concentrations. In 2006, 2 additional patients from this group presented low cobalamin concentrations. CONCLUSIONS: These results show the importance of determining PI together with PCA, since the presence of abnormal results in both tests, that is low PI and positive PCA, is the association that best identifies patients with a higher risk to decrease cobalamin concentrations during follow-up.

Lack of deleterious effect on bone mineral density of long-term thyroxine suppressive therapy for differentiated thyroid carcinoma.

The effect of subclinical hyperthyroidism on bone mineral density is controversial and could be significant in patients with differentiated thyroid carcinoma who receive suppressive doses of levothyroxine (LT4). To ascertain whether prolonged treatment with LT4 to suppress thyrotropin had a deleterious effect on bone mineral density and/or calcium metabolism in patients thyroidectomized for differentiated thyroid cancer we have performed a cross-sectional study in a group of 88 women (mean +/- SD age: 51 +/- 12 years) treated with LT4 after near-total thyroidectomy and in a control group of 88 healthy women (51 +/- 11 years) matched for body mass index and menopausal status. We determined calcium metabolism parameters, bone turnover marker N-telopeptide and bone mass density by dual-energy X-ray absorptiometry. No differences were found between patients and controls in calcium metabolism parameters or N-telopeptide except for PTH, which was significantly increased in controls. No differences were found between groups in bone mineral density in femoral neck (0.971 +/- 0.148 gr/cm(2) vs 0.956 +/- 0.130 gr/cm(2) in patients and controls respectively, P = 0.5). In lumbar spine, bone mineral density values were lower in controls than in patients (1.058 +/- 0.329 gr/cm(2) vs 1.155 +/- 0.224 gr/cm(2) respectively, P < 0.05). When premenopausal (n = 44) and postmenopausal (n = 44) patients were compared with their respective controls, bone mineral density was similar both in femoral neck and lumbar spine. The proportion of women with normal bone mass density, osteopenia and osteoporosis in patient and control groups was similar in pre- and postmenopausal women. In conclusion, long-term suppressive LT4 treatment does not appear to affect skeletal integrity in women with differentiated thyroid carcinoma.

Thrombomodulin and induced tissue factor expression on monocytes as markers of diabetic microangiopathy: a prospective study on hemostasis and lipoproteins in insulin-dependent diabetes mellitus.

Vascular complications are the main cause of morbidity in diabetes mellitus. To evaluate lipoprotein and hemostatic parameters and their relationship with clinically detectable microangiopathy, we studied 58 insulin-dependent diabetes mellitus patients and 60 controls matched for age, sex, and body mass index. Thirteen patients presented clinically detectable microangiopathy (8 retinopathy and 5 both retinopathy and microalbuminuria). A cross-sectional study of lipid profile, coagulation parameters, and a flow-cytometric evaluation of tissue factor expression in normal monocytes induced by patient plasma were performed. Patients were re-evaluated for microangiopathy in a 3-year median follow-up. Patients showed triglyceride enrichment in low (P = 0.00002) and high density lipoproteins (P = 0.004) and increased levels of D-dimer (P < 0.00001), prothrombin fragment 1 + 2 (P < 0.00001), and thrombin-antithrombin III complex (P = 0.0001). Patients with clinically detectable microangiopathy had increased type 1 plasminogen activator inhibitor (P = 0.00001), thrombomodulin (P = 0.02), and induced monocyte tissue factor expression (P < 0.00001). Nine patients developed clinically detectable microangiopathy in the follow-up and the only predictive variable was increased induced tissue factor expression. In conclusion, in these patients elevated thrombin and fibrin generation reflects a hypercoagulable state but clinically detectable microangiopathy seems related to endothelial cell injury markers and to increased induced tissue factor expression on monocytes.

Relationship between lipoprotein profile and urinary albumin excretion in type II diabetic patients with stable metabolic control.

OBJECTIVE: To assess lipids and lipoprotein composition and the relationship between lipoprotein abnormalities and urinary albumin excretion (UAE) in select type II diabetic patients with stable metabolic control. RESEARCH DESIGN AND METHODS: Fifty-five type II diabetic patients and 55 healthy control subjects both with a body mass index < 30 kg/m2 were studied. Patients were classified according to their level of UAE as normoalbuminuric (n = 37), microalbuminuric (n = 11), and macroalbuminuric (n = 7). In all cases, serum creatinine and albumin concentrations were in the normal range. RESULTS: Normoalbuminuric patients showed increased triglyceride (TG) contents in intermediate-density lipoprotein (IDL) (P < 0.01), low-density lipoprotein (LDL) (P < 0.001), and high-density lipoprotein (HDL) (P < 0.001) compared with control subjects. Lipoprotein concentration in microalbuminuric patients did not differ from that of normoalbuminuric patients. On the other hand, patients with macroalbuminuria showed a significant increase in IDL cholesterol (P < 0.01) and IDL (P < 0.01), LDL (P < 0.05), and HDL TGs (P < 0.01) compared with the other groups. Diabetic patients with nephropathy, both microalbuminuric and macroalbuminuric, tended to have higher mean lipoprotein(a) (Lp[a]) concentrations than normoalbuminuric patients and control subjects. A strongly positive correlation was observed between UAE and serum TGs (r = 0.56) and very-low-density lipoprotein (r = 0.55), IDL (r = 0.52), LDL (r = 0.54), and HDL TGs (r = 0.52). CONCLUSIONS: Lipoprotein alterations observed in diabetic patients, specifically IDL abnormalities and a tendency toward high Lp(a) levels, which are more marked in those with increased UAE, may contribute to the excess of cardiovascular disease in type II diabetic patients, particularly those with nephropathy.

Lipoprotein composition in the insulin-deficient non-acidotic phase of type I diabetic patients and early evolution after the start of insulin therapy.

Lipoproteins, including intermediate density lipoproteins and lipoprotein(a), and apolipoproteins A-I, B, C-II, C-III and E, were studied in 13 newly-diagnosed type I diabetic patients with severe insulinopenia without dehydration or acidosis. At baseline, the main finding was a significant increase in serum triglycerides due to raised triglyceride concentrations in all lipoproteins, particularly triglyceride-rich lipoproteins. Cholesterol concentrations were slightly increased in lipoproteins and led to a significant increase in serum cholesterol. Two days after the start of insulin therapy, lipoprotein profiles had normalized except for the LDL triglyceride contents, which remained significantly increased on the fifth day of treatment. No significant modifications were observed in lipoprotein(a), apolipoproteins A-I and E concentrations throughout the study. However, serum apolipoproteins B, C-II and C-III were increased at baseline and fell to normal levels 2 days after the start of insulin therapy. On the other hand, apolipoprotein C-II/C-III ratios in high and very low density lipoprotein, showed no significant differences at baseline compared with controls, suggesting that an apolipoprotein C-II deficiency or apolipoproteins Cs imbalance can be ruled out. In conclusion, significant lipoprotein abnormalities were observed in the insulin-deficient state of type I diabetes mellitus; insulin therapy normalizes the lipoprotein profile in two days, except for low density lipoprotein triglyceride contents which remain increased at the fifth day.

[The usefulness of the teriparatide acetate (Parathar) infusion test in the diagnosis of pseudohypoparathyroidism]. / Utilidad del test de infusión con acetato de teriparatida (Parathar) en el diagnóstico del seudohipoparatiroidismo.

In pseudohypoparathyroidism there is a resistance to the action of the parathormone in its target organs. Patients with this disease show clinical and laboratory data of hypoparathyroidism with normal or high levels of parathormone. Three types of pseudohypoparathyroidism are known according to the site in which the disorder is localized, within the complex formed by the cell receptor for the hormone and the adenylate cyclase systems of the cell membrane: Ia, Ib and II. The response of plasmatic and urinary cyclic AMP to the administration of parathyroid hormone may be useful to establish the type of pseudohypoparathyroidism presented in determined patients. Three cases of pseudohypoparathyroidism in whom an intravenous stimulation test with the synthetic 1-34 fragment of the human parathormone [teriparatid acetate (PARATHAR)] are presented. These patients were diagnosed according to the responses of cyclic AMP of type I pseudohypoparathyroidism. The methodology followed for the study and the results obtained are commented.

Calculated low-density lipoprotein cholesterol should not be used for management of lipoprotein abnormalities in patients with diabetes mellitus.

OBJECTIVE: To assess the validity of calculated low-density lipoprotein cholesterol by the Friedewald formula for management of lipoprotein abnormalities in patients with diabetes mellitus. RESEARCH DESIGN AND METHODS: Calculated LDL cholesterol by the Friedewald formula was compared with measured LDL cholesterol after separation by ultracentrifugation in 61 patients with type I diabetes, 50 patients with type II diabetes, and 116 healthy control subjects. RESULTS: Calculated LDL cholesterol coincided with measured LDL cholesterol, with < 10% error, in 54 (49%) patients with diabetes mellitus, and 85 (73%) control subjects. Calculated LDL cholesterol was overestimated, with an error of > or = 10% of measured LDL cholesterol in 39% of patients and 26% of control subjects, and underestimated in 13 and 1%, respectively. Despite a good correlation between calculated and measured LDL cholesterol, the intraclass correlation coefficients demonstrated a poor concordance between calculated and measured LDL cholesterol, both in patients and control subjects. When comparing the mean differences of calculated and measured LDL cholesterol for diabetic subjects versus control subjects, significantly greater differences in type II (but not type I) diabetic subjects were seen. CONCLUSIONS: Calculation of LDL cholesterol by the Friedewald formula may be inaccurate for assessment of cardiovascular risk in patients with type II diabetes and may not be appropriate for management of lipoprotein abnormalities in those diabetic patients.

Renal function changes in microalbuminuric normotensive type II diabetic patients treated with angiotensin-converting enzyme inhibitors.

OBJECTIVE: To determine the effects of captopril on microalbuminuria and renal function in normotensive type II diabetic patients. RESEARCH DESIGN AND METHODS: A total of 26 patients were randomized in two homogeneous groups for clinical and analytical data in a 6-mo follow-up study. Group A received captopril (initial dose: 12.5 mg daily, increased according to tolerance); group B was untreated. RESULTS: Microalbuminuria decreased only in the treated group at 6 mo (P = 0.044) and a significant (P = 0.027) mean percentage change on microalbuminuria excretion between the groups was observed. Filtration fraction decreased in group A (baseline: 0.23 +/- 0.03; 6 mo: 0.22 +/- 0.04) and increased in group B (baseline: 0.22 +/- 0.04; 6 mo: 0.25 +/- 0.04) with a significant mean percentage change between the groups at 6 mo (P = 0.032). The mean percentage change in microalbuminuria was significantly correlated with a mean percentage change in diastolic blood pressure throughout the trial. Neither metabolic control nor sodium or protein intake changed in either group during the trial. CONCLUSIONS: These results suggest that captopril can help arrest microalbuminuria in normotensive type II diabetic patients, with a decrease in diastolic blood pressure and filtration fraction after a 6-mo treatment.

Suppressive therapy with levothyroxine for solitary thyroid nodules.

OBJECTIVE: To evaluate the effect of treatment with TSH suppressive dose of levothyroxine in patients with benign thyroid nodules. DESIGN: Prospective randomized study. Group A (n = 20) patients received levothyroxine and group B (n = 20) patients did not. The dose of levothyroxine was adjusted to obtain an effective suppression of TSH. A clinical, analytical and morphological (with ultrasound) review was performed every 3 months. The mean +/- SD follow-up period was 10.6 +/- 2.2 months. PATIENTS: Forty euthyroid women with solitary thyroid nodule on palpation, cold on scintigraphy and cytologically benign without contraindication participated. MEASUREMENTS: At entry: biochemical and hormonal parameters, thyroid scintigraphy and thyroid ultrasonography. Every 3 months additional determinations of thyroid hormones and TSH levels were carried out, if necessary, to verify effective TSH suppression. Every 6 months thyroid ultrasound imaging was performed. RESULTS: Patients were euthyroid at entry into the study. The mean dose of levothyroxine necessary to obtain TSH suppression was 2.82 +/- 0.6 micrograms/kg/day. No significant modification in the thyroid nodule diameter (mean +/- SD 2.6 +/- 1.2 vs 2.5 +/- 1.2 cm) or in the thyroid nodule volume (10.3 +/- 11.9 vs 10.1 +/- 12.2 ml) were observed in group A. In group B the results were similar (2.8 +/- 0.9 vs 2.7 +/- 1.8 cm and 9.2 +/- 6.4 vs 9.2 +/- 9.5 ml, respectively). No differences were found in either group in the number of nodules that reduced significantly their volume (four and three, respectively). CONCLUSIONS: The suppressive therapy with levothyroxine was not effective in reducing nodule sizes in patients with solitary benign thyroid nodules.

Effect of chronic clonidine treatment on urinary growth hormone excretion and linear growth in children with short stature.

Eleven prepubertal children with short stature were treated with clonidine (0.15 mg/m2 daily) for a period of 1 year. The effect of this drug was evaluated on both clinical (growth velocity, height standard deviation scores for chronological age and bone age) and hormonal (urinary growth hormone excretion and insulin-like growth factor I) parameters. Our study shows that long-term clonidine administration in children with short stature did not result in significant differences in growth velocity, height standard deviation scores for chronological age and bone age, insulin-like growth factor I or in urinary growth hormone excretion.