Long-term course and predictive factors of elevated serum thyroglobulin and negative diagnostic radioiodine whole body scan in differentiated thyroid cancer.

UNLABELLED: Following the initial management, some patients with differentiated thyroid cancer (DTC) develop a state of high thyroglobulin (Tg) and negative diagnostic radioactive iodine (RAI) whole body scan (DxWBS). The predisposing factors and outcome of this condition are unclear. In this study, our objectives were to determine the predictive factors for the development of high Tg and negative DxWBS (Tg+/scan-) and to study the long-term course of the disease in patients with this condition. METHODS: We, retrospectively, reviewed the medical records of a cohort of 105 non-selected DTC patients (26 males and 79 females; median age 37.7 yr, range 7-72). None of these patients had positive Tg antibodies or distant metastases. All Tg levels were obtained off thyroid hormone therapy. At the first follow-up visit after RAI ablation (13 +/- 7.6 months), patients were classified into those with low Tg (<2 ng/ml off L-T4) and negative DxWBS (control group) and those with high Tg ( > or = 22 ng/ ml off L-T4) and negative DxWBS (Tg+/scan- group). Using univariate and multivariate logistic regression analyses, we evaluated a number of parameters (see results) for their association with the development of Tg+/scan-. In addition, the long-term course of the disease in Tg+/scan- group was analyzed. RESULTS: In univariate analysis, the following factors were found to be significantly associated with Tg+/scan-: perithyroidal tumor extension (p=0.025), soft tissue invasion (p=0.001), cervical lymph node metastases (p=0.014) and Tg level before RAI ablation (p=0.015). In multivariate analysis, only soft tissue invasion remained significantly associated with Tg+/scan- [p 0.001, odds ratio, 15.6 (95% Cl, 2.96-82.06)]. Age, sex, duration of goiter before surgery, pressure symptoms, tumor size, tumor multifocality, lymph nodedissection at initial surgery, tumor-node-metastasis (TNM) stage, and RAI ablative dose were not associated with Tg+/ scan-. In 53 patients with Tg+/scan-, 42 cases were followed without any therapeutic intervention; over a median follow-up of 71.6 months (range, 13-144.7), 31 cases had a spontaneous remission and 11 cases continued to have a persistent disease (Tg > or = 2 ng/ml, negative DxWBS, and no palpable disease or distant metastases); Tg declined from 9.32 +/- 9.91 ng/ml at first visit after RAI ablation to 1.59 +/- 5.39 ng/ml at last visit (p<0.0001). In the other 11 cases of Tg+/scan- group, one or more therapeutic interventions (RAI, surgery, or external radiotherapy) were undertaken. Over a median follow-up of 98.4 months (range, 6-147), Tg decreased from 110.2 +/- 147.5 to 23.5 +/- 41.2 ng/ml (p 0.026); 4 cases achieved remission, 5 cases continued to have persistent disease, and 2 cases had progression of their disease, which led to their death. CONCLUSION: Soft tissue invasion on original surgery strongly predicts the development of Tg+/scan- in DTC patients. The long-term course of the disease is mostly favorable especially when the Tg level is only modestly elevated.

Nephrolithiasis during pregnancy secondary to primary hyperparathyroidism.

Nephrolithiasis secondary to primary hyperparathyroidism infrequently complicates pregnancy. It can cause severe maternal and fetal complications. We present a case of a pregnant woman with nephrolithiasis and primary hyperparathyroidism. We reviewed the management of nephrolithiasis due to primary hyperparathyroidism during pregnancy. We believe that early recognition and timely intervention can significantly reduce the incidence of complications.

Life-threatening hypercalcemia associated with primary hyperparathyroidism during pregnancy: case report and review of literature.

OBJECTIVE: To report a case of life-threatening hypercalcemia attributable to primary hyperparathyroidism in a pregnant patient and discuss the management of severe hypercalcemia during pregnancy. METHODS: We describe a 28-year-old pregnant woman who had life-threatening hypercalcemia (serum calcium level of 25.8 mg/dL). Primary hyperparathyroidism was diagnosed. The patient's management and the published medical literature on primary hyperparathyroidism during pregnancy are reviewed. RESULTS: Our patient had the highest reported serum calcium level that we could find attributable to primary hyperparathyroidism during pregnancy. After initial stabilization, parathyroidectomy was successfully performed during pregnancy. To our knowledge, this is the first report in which this profound degree of hypercalcemia did not result in an adverse maternal or fetal outcome. CONCLUSION: Although uncommon, primary hyperparathyroidism during pregnancy may be associated with severe maternal and perinatal complications. Life-threatening hypercalcemia due to primary hyperparathyroidism during pregnancy can be successfully managed surgically during pregnancy, with good maternal and fetal outcome.

The syndrome of resistance to thyroid hormone, misdiagnosed and treated as thyrotoxicosis.

OBJECTIVE: To report two cases of resistance to thyroid hormone and to promote increased awareness of this syndrome, which is frequently misdiagnosed and incorrectly treated. METHODS: We describe a young woman and her father, both of whom were diagnosed at a younger age as having thyrotoxicosis and were treated with thyroidectomy and radioactive iodine. Both patients later proved to have resistance to thyroid hormone and required supraphysiologic doses of levothyroxine to normalize the thyroid-stimulating hormone (TSH) while remaining euthyroid. RESULTS: Laboratory evaluation revealed increased serum total thyroxine and triiodothyronine levels as well as normal to increased TSH levels. The free alpha sub-unit/TSH ratio was normal, and magnetic resonance imaging of the pituitary gland showed no tumor. Metabolic studies in the daughter, with use of graded doses of triiodothyronine, supported the diagnosis. CONCLUSION: Both patients shown to have resistance to thyroid hormone were misdiagnosed and inappropriately treated in the past. The resultant hypothyroidism has been difficult to treat, particularly in the father who has coronary artery disease.

Gestational diabetes: should it be added to the syndrome of insulin resistance?

OBJECTIVE: The significance of gestational diabetes mellitus (GDM) results from its short-term detrimental effects on the fetus and its long-term prediction of NIDDM in the mother. We compared several variables associated with insulin resistance between GDM and non-GDM pregnant women to show the similarities between GDM and NIDDM (and thus insulin resistance). RESEARCH DESIGN AND METHODS: On the basis of a 3-h oral glucose tolerance test (OGTT), 52 GDM patients and 127 non-GDM patients were recruited from pregnant, non-diabetic women who had a nonfasting 1-h-50-g glucose screening test > or = 7.2 mmol/l (130 mg/dl) performed between 16 and 33 weeks of gestation (a total of 518 of 3,041 women drawn from six community health care prenatal clinics were screened positive). During the OGTT, several potential markers of insulin resistance were measured at fasting and 2-h time points, in addition to the standard glucose measurements. The relationship of these variables with the diagnosis of GDM was studied. RESULTS: GDM patients, compared with non-GDM patients, had 1) higher prepregnancy weight (P = 0.011), prepregnancy BMI (P = 0.006), C-peptide at fasting (P = 0.002) and at 2 h (P < 0.001), insulin at fasting (P = 0.001) and at 2 h (P < 0.001), triglycerides at fasting (P = 0.005) and at 2 h (P = 0.003), free fatty acids at fasting (P = 0.017), beta-hydroxybutyrate at fasting (P = 0.007); and 2) lower HDL cholesterol at fasting (P = 0.029). These variables were all predictive of GDM (P < 0.036) individually. Using stepwise logistic regression with all of these variables available, fasting (P = 0.019) and 2-h (P < 0.001) insulin levels, fasting free fatty acids (P = 0.031), and fasting beta-hydroxybutyrate (P = 0.036) were statistically significant as jointly predictive of GDM. Comparisons between GDM patients and non-GDM patients matched by BMI confirmed that the metabolic abnormalities persisted when difference in BMI was taken into account. Concomitant blood pressure measurements in women with GDM did not differ significantly from those without GDM. CONCLUSIONS: Our results show that many of the known metabolic components of the syndrome of insulin resistance (syndrome X) are predictive of GDM. These results are in keeping with the argument that GDM is one phase of the syndrome of insulin resistance. We suggest that GDM be looked upon as a component of the syndrome of insulin resistance that provides an excellent model for the study and prevention of NIDDM in a relatively young age-group.