Visceral fat mass as a novel risk factor for predicting gestational diabetes in obese pregnant women.

OBJECTIVE: To develop a model to predict gestational diabetes mellitus incorporating classical and a novel risk factor, visceral fat mass. METHODS: Three hundred two obese non-diabetic pregnant women underwent body composition analysis at booking by bioimpedance analysis. Of this cohort, 72 (24%) developed gestational diabetes mellitus. Principal component analysis was initially performed to identify possible clustering of the gestational diabetes mellitus and non-GDM groups. A machine learning algorithm was then applied to develop a GDM predictive model utilising random forest and decision tree modelling. RESULTS: The predictive model was trained on 227 samples and validated using an independent testing subset of 75 samples where the model achieved a validation prediction accuracy of 77.53%. According to the decision tree developed, visceral fat mass emerged as the most important variable in determining the risk of gestational diabetes mellitus. CONCLUSIONS: We present a model incorporating visceral fat mass, which is a novel risk factor in predicting gestational diabetes mellitus in obese pregnant women.

Pregnancy outcomes in women with gestational diabetes treated with metformin or insulin: a case-control study.

AIMS: To compare maternal and neonatal outcomes in women with gestational diabetes mellitus (GDM) treated with either metformin or insulin. METHODS: One hundred and twenty-seven women with GDM not adequately controlled by dietary measures received metformin 500 mg twice daily initially. The dose was titrated to achieve target blood glucose values. Pregnancy outcomes in the 100 women who remained exclusively on metformin were compared with 100 women with GDM treated with insulin matched for age, weight and ethnicity. RESULTS: There were no significant differences in baseline maternal risk factors. Women treated with insulin had significantly greater mean (sem) weight gain from enrolment to term (2.72 +/- 0.4 vs. 0.94 +/- 0.3 kg; P < 0.001). There was no difference between the metformin and insulin groups, respectively, comparing gestational hypertension (6 vs. 7%, P = 0.9), pre-eclampsia (9 vs. 2%, P = 0.06) induction of labour (26 vs. 24%, P = 0.87) or rate of Caesarean section (48 vs. 52%, P = 0.67). No perinatal loss occurred in either group. Neonatal morbidity was improved in the metformin group; prematurity (0 vs. 10%, P < 0.01), neonatal jaundice (8 vs. 30%, P < 0.01) and admission to neonatal unit (6 vs. 19%, P < 0.01). The incidence of macrosomia (birthweight centile > 90) was not significantly different [metformin (14%) vs. insulin (25%); P = 0.07]. CONCLUSIONS: Women with GDM treated with metformin and with similar baseline risk factors for adverse pregnancy outcomes had less weight gain and improved neonatal outcomes compared with those treated with insulin. Diabet. Med. 26, 798-802 (2009).

Differentiated thyroid cancer presenting with thyrotoxicosis due to functioning metastases.

Thyrotoxicosis due to functioning metastases in differentiated thyroid cancer (DTC) is exceedingly rare. We report a case of follicular carcinoma in a 54-year-old manager, who presented with thyrotoxicosis, shortness of breath and lung metastases. Transbronchial biopsy of a pulmonary nodule demonstrated normal thyroid. This was interpreted as representing very well-differentiated thyroid cancer. CT, (131)I whole-body imaging and dosimetry is described following total thyroidectomy and repeated radioiodine administration (cumulative activity 34.6 GBq). The patient became asymptomatic with almost complete eradication of the pulmonary metastases. Potential complications of thyroid storm, bone marrow failure and pulmonary fibrosis following radioiodine are discussed, together with methods to minimise these risks.

Glomerular filtration rate is a major determinant of the relationship between 25-hydroxyvitamin D and parathyroid hormone.

The reference range for 25-hydroxyvitamin D (25-OHD) remains uncertain, and it is not clear as to whether interpretation of circulating 25-OHD would be aided by simultaneous measurement of serum parathyroid hormone (PTH). We wanted to define the level of serum 25-OHD associated with a raised serum PTH and to examine the determinants of the relationship between serum 25-OHD and serum PTH concentration. We retrospectively examined data for patients who had a 25-OHD measurement and other biochemical variables over a 12-month period in our center. We found that 28% of patients had a serum 25-OHD level below 50 nmol/L and serum PTH level in the normal reference range, whereas 24% had a serum 25-OHD level below 50 nmol/L with a serum PTH value above the normal reference range. At a serum 25-OHD level of 80 nmol/L, 1.5% had an elevated serum PTH and, at 50 nmol/L, 8% had raised serum PTH. Further examination showed that for patients with low serum 25-OHD, low glomerular filtration rate (GFR) was a major determinant of the PTH response. These data confirm an inverse correlation between serum 25-OHD and serum PTH. Minimal numbers of patients (1.5% of the study group) have a raised serum PTH at a serum 25-OHD level of 80 nmol/L. GFR is a major determinant of the PTH response to decreasing serum levels of 25-OHD.

Salivary gland toxicity after radioiodine therapy for thyroid cancer.

AIMS: Salivary gland toxicity is a common, but not widely appreciated, adverse effect of high-dose radioiodine (131I). This study was carried out to determine the incidence of symptoms of salivary gland damage after 131I treatment for differentiated thyroid cancer. MATERIALS AND METHODS: This was a prospective study of 76 consecutive patients attending thyroid cancer treatment. Symptoms of salivary gland damage (dry mouth, pain and swelling) were assessed during hospital admission and at follow-up visits. Additionally, a retrospective analysis was carried out of patients recorded in our database as having chronic salivary gland swelling after 131I ablation. RESULTS: Twenty patients (26%) developed salivary gland toxicity, 11 (15%) had symptoms within the first 48 h, continuing for 12 months in seven of these patients. The onset of toxicity in a further nine (12%) patients with persistent symptoms did not occur until 3 months after therapy. In total, 16 (21%) patients had evidence of chronic toxicity, typically xerostomia, at 12 months. Toxicity was more common after repeated 131I administration. After searching our thyroid cancer database, we identified an additional five patients to have chronic salivary gland swelling (chronic sialadenitis or pleomorphic adenoma) 20 months to 23 years after 131I. CONCLUSIONS: Pain, swelling and dry mouth occurred frequently after 131I, with some developing symptoms months or years after administration. Early recognition of salivary gland complications may help to reduce morbidity in these patients.

Familial medullary thyroid cancer: clinical aspects and prognosis.

OBJECTIVE: To assess clinical features and long-term results of treatment of familial medullary thyroid carcinoma (FMTC). DESIGN: Retrospective analysis of all patients with familial forms of MTC diagnosed between 1949-2000 and treated in our unit. RESULTS: Fifty five patients (25 males, 30 females) were identified with at least two first-degree relatives affected by medullary thyroid cancer; 26 were classified as MEN 2A, 1 as MEN 2B and 28 as FMTC. Median age at diagnosis was 35 years (MEN 2A), 25 (MEN 2B) and 47.5 (FMTC). Median follow-up was 9 years (range: 4-24). Total or near-total thyroidectomy was performed in all patients and 11 received adjuvant external beam radiotherapy. Cause specific survival was 89% at 10 years and 77% at 20 years for MEN patients, 51% and 32% for those with sporadic MTC, and 46% and 26% for those with FMTC. In multivariate analysis, factors predicting survival were presence of metastases, nodal status and age at diagnosis. CONCLUSIONS: Improved survival rates associated with familial types of MTC can be accounted for by the earlier stage at which disease is detected and the younger age at presentation. These observations emphasize the need for early detection in those at risk.

Prognosis for fertility and ovarian function after treatment with radioiodine for thyroid cancer.

The aim of this study was to review the outcome of ablative radioiodine treatment on ovarian function in young women treated for differentiated thyroid carcinoma. Of 1398 patients with differentiated thyroid cancer, 496 were women under the age of 40 at the time of diagnosis who had received radioiodine therapy. Of these, 322 received a single 3 GBq ablation dose of radioiodine while the remainder received subsequent treatment with (131)I with a cumulative activity of 8.5-59 GBq for residual, recurrent, or metastatic disease. Transient amenorrhoea or menstrual irregularities lasting up to 10 months were experienced in 83 patients (17%). No cases of permanent ovarian failure were recorded. There were 427 children born to 276 women; only one patient wishing to achieve a successful pregnancy outcome has been unsuccessful. Four premature births and 14 miscarriages occurred but no congenital abnormalities were reported. The risk of permanent damage to the ovaries after ablative radioiodine treatment appears to be low and patients can be reassured they can have normal pregnancies after this treatment.

Medullary thyroid cancer: multivariate analysis of prognostic factors influencing survival.

AIMS: The aims of this study were to assess the long-term results of treatment of medullary thyroid carcinoma (MTC) and to define prognostic factors. METHODS: Retrospective analysis of all patients diagnosed with MTC between 1949 and 1998 and treated in our unit was carried out. RESULTS: One hundred and sixty-two patients (87 females, 75 males) were identified; 52 patients (32%) had familial disease. Median follow-up was 9 years (2-20 years). The majority of patients (90%) presented with a thyroid mass or enlarged neck nodes. Total/subtotal thyroidectomy was performed in 129/18 patients respectively; 45 patients also underwent neck dissection while 52 had simple nodal excision. External beam radiotherapy (RT) was given to 76 patients with advanced disease at presentation. Overall survival was 72% at 5 years and 56% at 10 years; case-specific survival was very similar. In multivariate analysis the factors which were significant predictors of survival were age at diagnosis, extent of nodal disease, extent of surgery and metastases at presentation. RT significantly reduced local relapse in patients with ipsilateral nodal disease. CONCLUSIONS: MTC may be associated with prolonged survival; the best prognosis occurs in young patients undergoing total thyroidectomy and neck dissection. External beam RT significantly reduces local relapse in patients with limited nodal disease.

Failure of TSH rise prior to radio-iodine therapy for thyroid cancer: implications for treatment.

We describe three patients with well-differentiated thyroid carcinoma in whom no rise in serum thyroid-stimulating hormone (TSH) was observed after the discontinuation of thyroid hormone. In one patient, TSH deficiency was due to panhypopituitarism secondary to the empty sella syndrome. This patient initially failed to respond to (131)I but was subsequently given purified porcine TSH prior to further (131)I therapy. This resulted in a significant fall in the thyroglobulin level. In two further patients, TSH levels were suppressed by functioning follicular thyroid cancer. There was an unexpectedly good (131)I uptake by metastases and they responded clinically. The failure of TSH levels to rise after thyroid hormone withdrawal should prompt investigation of the pituitary-thyroid axis. In patients with hypopituitarism, exogenous TSH is recommended, to increase the (131)I uptake. In contrast, when TSH is suppressed by functioning tumour, radio-iodine treatment may still be effective.

Good prognosis in thyroid cancer found incidentally at surgery for thyrotoxicosis.

An analysis of the outcome of thyroid carcinoma incidentally discovered in patients undergoing surgery for hyperthyroidism is presented. Among 986 patients with differentiated thyroid cancer, 23 had presented with symptoms and signs of hyperthyroidism. Graves' disease was diagnosed in 11, multinodular goitre in eight and toxic adenoma in four. Following thyroidectomy, histology revealed papillary (18), follicular (four) and Hurthle cell (one) carcinoma. Tumour size ranged from 4 mm to 5.5 cm, multifocality was detected in three patients, and lymph node involvement in one. Two patients (one with associated Graves' disease, one with multinodular goitre) relapsed locally and required further surgery; one developed distant metastases and died 7 years after initial presentation. Two patients died of unrelated causes; the remaining 20 patients are alive and well with a median follow-up of 16 (1-34) years. Differentiated thyroid cancer found incidentally at surgery for hyperthyroidism has a good prognosis.

Management of differentiated thyroid cancer diagnosed during pregnancy.

OBJECTIVE: To assess the outcome of thyroid cancer diagnosed during pregnancy. DESIGN: Retrospective analysis of patients diagnosed between 1949 and 1997 with thyroid cancer presenting during pregnancy. RESULTS: Nine women with a median age of 28 years were identified. A thyroid nodule was discovered by the clinician during routine antenatal examination in four cases, the remainder had noted a lump in the neck. In all patients, the nodule was reported to almost double in size during the pregnancy. One patient underwent subtotal thyroidectomy during the second trimester; eight were operated on within 3 to 10 months from delivery. Total thyroidectomy was performed in five and subtotal thyroidectomy in four. All tumours were well differentiated and ranged in size from 1 to 6 cm. OUTCOME: The median follow-up was 14 years (5-31 years). One patient relapsed locally requiring further surgery. One patient developed bone metastases dying 7 years after presentation; her planned treatment had been delayed because of an intervening pregnancy. Eight of the original cohort of patients are currently disease free. CONCLUSIONS: Differentiated thyroid cancer presenting in pregnancy generally has an excellent prognosis. When the disease is discovered early in pregnancy, surgery should be considered in the second trimester but radioiodine scans and treatment can be safely delayed until after delivery. In all cases, treatment should not be delayed for more than a year.

Long-term glycaemic control directly correlates with glomerular filtration rate in early Type 1 diabetes mellitus before the onset of microalbuminuria.

Hyperfiltration occurs early in diabetes mellitus and has been implicated in the development of microalbuminuria. Our aim was to re-examine the controversial relationship between glycaemic control and glomerular filtration (GFR) in normoalbuminuric, normotensive, non-obese patients with short duration Type 1 diabetes mellitus (DM). We studied 75 Type 1 DM patients, 35 male, aged 18-42 years, with a duration of diabetes of 4-8 years. GFR was determined by inulin clearance; hyperfiltration was defined as above 145 ml min(-1) 1.73 m(-2) (equivalent to 2 SD above mean for a control population). Analysis was by paired Student's t-testing and linear regression. GFR correlated significantly with HbA1c (r= 0.47, p < 0.0001) and fructosamine (r= 0.24, p = 0.035). Mean HbA1c and fructosamine in the 13 patients with hyperfiltration was significantly higher than in the rest of the group (HbA1c: 9.2% (95% C.I. 7.9-10.4%) vs 7.6 % (7.2-7.9), p= 0.002; fructosamine: 479 micromol l(-1) (450-507) vs 410 micromol l(-1) (388-432), p = 0.009. This significant difference persisted even when the two highest values of HbA1c or fructosamine were removed from analysis. Effective renal plasma flow, assessed by PAH clearance, also correlated in all patients with HbA1c (r=0.31, p=0.039). We conclude that poor glycaemic control directly correlates with hyperfiltration and renal hyperperfusion in early Type 1 DM.

Rapid progression of fibrosing alveolitis and thyrotoxicosis after antithymocyte globulin therapy for aplastic anemia.

Antithymocyte globulin (ATG) therapy is an established form of treatment for aplastic anaemia and has also been used as prophylaxis against graft rejection of bone marrow and renal allografts. Administration of ATG preparations has been associated with many mild clinical reactions, as have other forms of immunomodulatory therapy. However, serious adverse effects appear to be rare. We report a case of rapidly progressive fibrosing alveolitis and thyrotoxicosis in relation to ATG therapy, highlighting its potential toxicity and emphasising that its administration should be undertaken by experienced physicians in specialised centres.

Bone mineralization after treatment of growth hormone deficiency in survivors of childhood malignancy.

Having noted symptomatic osteoporotic vertebral collapse in young adult survivors of childhood malignancy, bone mineral density (BMD) was examined at three sites by dual-energy X-ray absorptiometry in 64 patients treated in childhood for intracranial malignancy (group 1; n = 21) or acute leukaemia (group 2; n = 43). Patients in group 1 were selected for growth hormone deficiency (GHD) by auxological and biochemical criteria before the end of puberty (Tanner stage V). Seven patients (six men; mean (+/- SEM) age at study, 28.0 +/- 2.9 years; mean age at diagnosis, 8.7 +/- 1.5 years) in this group had been treated with human pituitary growth hormone (GH) for 1-12 years; and 14 patients (nine men; mean age at study, 26.8 +/- 1.0 years; mean age at diagnosis, 10.7 +/- 1.4 years) had not received GH. Bone densities in group 1 were normal in the GH-treated patients at the femoral neck (98.4 +/- 3.8% of control), lumbar spine (100.4 +/- 6.1% of control) and Ward's triangle (101.0 +/- 6.1% of control) but markedly reduced in the untreated group (femoral neck, 81.2 +/- 2.6% of control (p = 0.002); lumbar spine, 79.1 +/- 4.1% of control (p = 0.04); Ward's triangle, 80.1 +/- 3.6% of control (p = 0.01)). The majority of patients in group 2 had been treated for acute lymphoblastic leukaemia (ALL) and were in three subgroups.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone deficiency during puberty reduces adult bone mineral density.

Bone mineral density (BMD) was evaluated by dual energy x ray absorptiometry in 60 adults (33 males, 27 females; aged 50, range 23-76 years) who were growth hormone deficient from various causes for 10.4 (1-31) years. Adult patients who had acquired growth hormone deficiency before completion of puberty had significantly reduced mean (SEM) BMD compared with age matched healthy controls at the lumbar spine: 0.87 (0.09) v 1.20 (0.03) g/cm2, femoral neck: 0.81 (0.06) v 1.08 (0.04) g/cm2, and Ward's triangle: 0.68 (0.07) v 1.04 (0.05) g/cm2. These values were also reduced compared with those of patients who had received human growth hormone during puberty. Untreated growth hormone deficiency when present during puberty results in reduced adult bone density.