Philippe Hagag

Hypothyroidism following partial thyroidectomy

Objective To compare rates of hypothyroidism following three types of partial thyroidectomy for multinodular goiter. Study Design and Methods All cases of partial thy-roidectomies (hemi-, near-total, or subtotal) carried out at one Israeli and one Russian medical center (1990–2006) were retrospectively studied to determine the incidence of hypothyroidism after each procedure. Results There were 881 near-total, 1538 subtotal, and 1051 hemithyroidectomies (total 3470). Postoperative follow-up was 2 to 15 years. Twenty-eight percent of the hemithyroidectomy patients suffered permanent hypothyroidism compared to 100% of the near-total and 87% of the subtotal patients. Forty-six percent of the hemithyroidectomy patients suffered temporary hypothyroid-ism compared to 100% of the near-total and 93% of the subtotal patients. Conclusion Subtotal and near-total thyroidectomies produced a rate of hypothyroidism close to that of total thyroidectomy compared to 28% after hemithyroidectomy. Significance Partial thyroidectomies provide no decisive advantage over total thyroidectomies in terms of subsequent requirements of supplemental hormone therapy.

Early postmenopausal bone loss in hyperthyroidism

OBJECTIVES To evaluate the effect of hyperthyroidism on bone in relation to the menopausal state. METHODS Fifty-nine hyperthyroid (HYPER), 40 hypothyroid (HYPO), and 51 control euthyroid (EUTH) women were studied. Bone mineral density (BMD) was assessed by dual X-rays absorptiometry (DXA) at the lumbar spine, and at the femoral neck. A multi-site QUS device evaluated speed of sound (SOS) at the radius (RAD), tibia (TIB), metatarsus (MTR), and phalanx (PLX). Bone markers used were serum bone specific alkaline phosphatase (BSAP) and urinary deoxypyridinoline (DPD). RESULTS At all sites, SOS was lower in HYPER than in EUTH (RAD P<0.05, TIB P<0.01, MTR P<0.05, PLX P=0.01). The low SOS was only noted at the early postmenopausal period. BMD at the femoral neck but not at the lumbar spine was lower in HYPER as compared to EUTH (P<0.05). Both femoral neck and tibia were the sites with the highest odds ratio for being hyperthyroid (2.3 and 2.04, respectively). There was no correlation between BMD or SOS and FT(4), TT(3) or duration of hyperthyroidism. BSAP and DPD positively correlated with FT(4) and TT(3) (P<0.05). CONCLUSIONS This study suggests that hyperthyroidism affects bone mineralization especially during the early postmenopausal period, and the effect is mainly at the cortical bone.

Follicular variant of papillary thyroid carcinoma: clinical-pathological characterization and long-term follow-up.

PURPOSEQuestions arise concerning the behavior and prognosis of the follicular variant of papillary thyroid carcinoma. PATIENTS AND METHODSBetween 1990 and 2003, 92 patients with follicular variant of papillary carcinoma (group A) were enrolled in a long-term study and compared with control groups of follicular thyroid carcinoma (group B, 40 cases) and pure papillary thyroid carcinoma (group C, 99 subjects). RESULTSGender (female/male), age, and follow-up duration (years, mean ± standard error) in groups B, A, and C were 36/4, 43 ± 3, 11 ± 1.1; 79/13, 46 ± 2, 9.5 ± 0.7; and 82/17, 44 ± 1, 10 ± 0.6, respectively. At the time of diagnosis, the rates of extensive extra thyroidal local spread, bilateral lesions, and vascular invasion were higher in group A than in group C. The rate of metastasis tumors was higher in group A than in group C and was comparable in groups A and B. Complete remission was reported in 95% of group B patients, 98% of group C individuals, and in only 77% of group A subjects. Persistent stable lesions and progressive disease rates in groups B, A, and C were 2.5% and 2.5%, 15% and 8%, and 0% and 2%, respectively. The survival rates at the end of the study were 100% in all cohorts, but the cumulative dose of administered radioiodine in group A was higher than in group C and was comparable to that given in group B. Metastases dedifferentiation was observed only in the group A (three patients). DISCUSSIONFollicular variant of papillary thyroid carcinoma may be more aggressive than previously considered and should be clearly distinguished from the two other forms of well-differentiated thyroid carcinoma.

Discordant effect of body mass index on bone mineral density and speed of sound

BackgroundIncreased BMI may affect the determination of bone mineral density (BMD) by dual X-ray absorptiometry (DXA) and speed of sound (SOS) measured across bones. Preliminary data suggest that axial SOS is less affected by soft tissue. The purpose of this study is to evaluate the effect of body mass index (BMI) on BMD and SOS measured along bones.MethodsWe compared axial BMD determined by DXA with SOS along the phalanx, radius and tibia in 22 overweight (BMI > 27 kg/m2), and 11 lean (BMI = 21 kg/m2) postmenopausal women. Serum bone specific alkaline phosphatase and urinary deoxypyridinoline excretion determined bone turnover.ResultsMean femoral neck – but not lumbar spine BMD was higher in the overweight – as compared with the lean group (0.70 ± 0.82, -0.99 ± 0.52, P < 0.00001). Femoral neck BMD in the overweight – but not in the lean group highly correlated with BMI (R = 0.68. P < 0.0001). Mean SOS at all measurement sites was similar in both groups and did not correlate with BMI. Bone turnover was similar in the two study groups.ConclusionsThe high BMI of postmenopausal women may result in spuriously high BMD. SOS measured along bones may be a more appropriate means for evaluating bones of overweight women.

Diagnosis of normocalcemic hyperparathyroidism by oral calcium loading test

We evaluated the oral calcium-loading test (OCLT) in diagnosing normocalcemic primary hyperparathyroidism. Calcium and PTH levels were measured before, 60, 120 and 180 min after oral 1 g of calcium gluconolactate administration in 102 consecutive females with high circulating PTH levels, and 25 controls. Patients were classified as follows: Group A, patients with a parathyroid adenoma identified by two imaging modalities. Sub-Group AO, hyper-parathyroid patients [no.=13, mean age 59 yr (SD=10)] evaluated prior to parathyroidectomy. Sub-Group AH, non-operated hypercalcemic patients [no.=29, age 63 yr (SD=11)]. Sub-Group AN, normocalcemic non-operated women [no.=14, age 59 yr (SD=8)]. Group B, normo-calcemic individuals [no.=46, age 58 yr (SD=11)] with negative parathyroid imaging. Group C, control patients [no.= 25, age 56 yr (SD= 12)]. The concentrations of calcium and PTH overlapped in the normocalcemic groups during the OCLT. Product P, defined as circulating PTH nadir (pg/ml) × peak calcium concentration (mg/dl), better discriminated Sub-Group AN from Group B, AUC=0.98 (95% CI 0.95, 1.00) than did Ratio R, defined as relative PTH decline/relative calcium increment, AUC= 0.86 (95%CI 0.73, 0.99). Assuming normal threshold of Product P and Ratio R at 260 and 17 respectively, the combined parameters diagnose normocalcemic hyperparathyroid patients with 100% sensitivity and 87% specificity.

Role of colestipol in the treatment of hyperthyroidism

The enterohepatic circulation of thyroxine (T4) and triiodothyronine (T3) is higher in thyrotoxicosis. Bile-salt sequestrants bind iodothyronines and thereby increase their fecal excretion. We, therefore, evaluated the effect of colestipol-hydrochloride administration on clinical and biochemical indices of patients with hyperthyroidism. In a prospective, controlled trial, ninety-two adult volunteers with Graves’ disease, toxic autonomous nodule or toxic multinodular goiter were randomly assigned into the following treatment protocols: Group 1, 30 mg of methimazole (MMI) and 20 g of colestipol-hydrochloride (COL) daily; Group 2, 30 mg of MMI daily; and Group 3, 15 mg of MMI 20 g of COL daily. The patients were further classified into Group A, severe hyperthyroidism (baseline levels of total T3 (TT3) ≥5nmol/l) and Group B, mild to moderate thyrotoxicosis (baseline levels of TT3<5 nmol/l). Crook’s clinical index, serum free T4 (FT4), TT3 and thyroid stimulating hormone (TSH) levels were determined before (W0), following one week (W1) and two weeks (W2) of treatment. Serum TT3 level decreased (mean±SE) at W1 by 40.8±2.6% of W0 in Group 1 and by 29.2±2.4% in Group 2 (p<0.001), and down further to 47.8±3.0% at W2 in Group 1, and 40.6±2.8% in Group 2 (p=0.01). Serum FT4 level decreased (mean±SE) from W0 to W1 by 31.7±2.7% in Group 1 and by 16.2±3.1% in Group 2 (p=0.005), and down to 49.1±2.8% of W0 at W2 in Group 1 and to 38.7±3.5% in Group 2 (p=0.07). In sub groups B COL was not effective in reducing thyroid hormone levels nor in ameliorating the clinical status of the patients. However, in Group A3 COL lowered FT4 (p=0.001) and TT3 (p=0.05) levels as compared to group A2. At W2 the clinical hyperthyroidism score improved faster in Group A1 (p<0.001) and Group A3 (p=0.012) as compared to the control Group A2. In conclusion, COL is an effective and well tolerated adjunctive agent in the treatment of hyperthyroidism. Its main effect is in severe cases of thyrotoxicosis, and in the first phase of treatment. As adjunctive COL treatment in hyperthyroidism allows reducing MMI dosage it may decrease the rate of dose dependent MMI side effects.

Effect of estrogen replacement therapy on speed of sound at multiple skeletal sites

OBJECTIVES To evaluate the effect of estrogen replacement therapy (ERT) on postmenopausal bone loss by multi-site ultrasound measurement. METHODS A cross-sectional comparison of postmenopausal women, ERT users and non-users. The two study groups were enrolled for the reference database collection for the Sunlight Omnisense (Omnisense) and were matched by years since menopause. Speed of sound (SOS) was measured at the distal radius (RAD), mid-shaft tibia (TIB), fifth metatarsus (MTR) and proximal phalanx (PLX). RESULTS 143 ERT users for 5.2+/-3.6 years were compared with 139 ERT non-users (age: 57.0+/-5.3 and 57.5+/-5.5, respectively). Both groups were 7.1+/-5.0 years since menopause. SOS, expressed in T-score units, was higher at the RAD in ERT users as compared to ERT non-users (-0.55+/-1.30 and -1.36+/-1.60, respectively, P<0.0001), and at the TIB (-0.73+/-1.34 and -1.28+/-1.45, respectively, P=0. 003). Same trend was observed at the MTR and PLX, but not statistically significant because of fewer observations. In early post menopause period, the ERT-non users RAD data shows an annual SOS decrease of 0.17 versus annual increase of 0.12 T-score units (P=0.037). Similar effect is observed at the TIB, though not statistically significant (non-users decrease of 0.20 vs. users increase of 0.08 T-score units/year, P=0.086). CONCLUSIONS SOS measurements by Omnisense at multiple skeletal sites support the ERT protective effect on bone.