Comparative evaluation of recombinant human thyrotropin-stimulated thyroglobulin levels, 131I whole-body scintigraphy, and neck ultrasonography in the follow-up of patients with papillary thyroid microcarcinoma who have not undergone radioiodine therapy.

CONTEXT: Although the prognosis of papillary thyroid microcarcinoma (PTMC) is usually excellent, the optimal follow-up strategy has never been investigated. OBJECTIVE: The objective of the study was to investigate the role of neck ultrasonography (US), whole-body scintigraphy (WBS), and serum thyroglobulin levels (Tg) after recombinant human (rh) TSH in the follow-up of very low-risk PTMC patients. DESIGN: The study was a 5-yr observational study based on a 6- to 12-month follow-up after near total thyroidectomy. SETTING: The study population consisted of ambulatory patients. PATIENTS: Eighty consecutive patients diagnosed with PTMC, who had not undergone postoperative radioiodine treatment because of unifocal tumor without lymph node metastases and who did not have anti-Tg antibodies, were included. MAIN OUTCOME MEASURES: WBS and Tg after both rhTSH and neck US were measured. RESULTS: rhTSH-Tg was 1 ng/ml or less in 45 (Tg-) and more than 1 in 35 (Tg+) patients. WBS showed no pathological uptake in any patient. US identified node metastases in two Tg (+) and one Tg (-) patients. rhTSH-Tg levels positively correlated with thyroid bed iodine uptake (r = 0.40, P < 0.0001). To date (32 +/- 13 months after surgery), all node-negative patients have undetectable Tg levels on LT(4) treatment and negative US. CONCLUSIONS: For the initial follow-up of PTMC patients without risk factors and anti-Tg antibodies and who did not undergo radioiodine treatment: 1) WBS is useless; 2) US is highly sensitive in detecting node metastases; and 3) detectable rhTSH-Tg levels mainly depend on small normal tissue remnants. In this subgroup of PTMC patients, neck US might be regarded as a primary tool for the initial follow-up.

Increased urinary albumin excretion, insulin resistance, and related cardiovascular risk factors in patients with type 2 diabetes: evidence of a sex-specific association.

OBJECTIVE: While the relevant role of insulin resistance in the pathogenesis of increased urinary albumin excretion (UAE) is well established in type 1 diabetes, its contribution in type 2 diabetes is controversial. Our aim was to investigate whether insulin resistance was associated with increased UAE in a large cohort of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 363 men and 349 women, aged 61 +/- 9 years, with a disease duration of 11 +/- 9 years and HbA(1c) levels of 8.6 +/- 2.0% were included. Insulin resistance was derived from the homeostasis model assessment of insulin resistance (HOMA(IR)), and UAE was derived from the albumin-to-creatinine ratio (ACR) defined as increased if the value was > or =2.5 mg/mmol in men and > or =3.5 mg/mmol in women. ACR was correlated with HOMA(IR) (r = 0.15, P = 0.0001), independently of age, disease duration, blood pressure, HbA(1c), triglycerides, waist circumference, and smoking. RESULTS: When the two sexes were investigated separately, a significant correlation between ACR and HOMA(IR) was reached in men (n = 363; r = 0.21, P = 0.0001) but not women (n = 349; r = 0.08, P = 0.14), suggesting that insulin resistance and sex may interact (P for interaction = 0.04) in determining UAE. When men were subgrouped into quartiles of HOMA(IR), those of the third and fourth quartile (i.e., the most insulin resistant) were at higher risk to have increased ACR than patients of the first quartile (third quartile: odds ratio 2.2 [95% CI 1.2-4.2], P = 0.01) (fourth quartile: 4.1 [2.2-7.9], P = 0.00002). Finally, ACR was significantly higher in men with two or more insulin resistance-related cardiovascular risk factors (i.e., abdominal obesity, dyslipidemia, and arterial hypertension) than in men with fewer than two insulin resistance-related cardiovascular risk factors (0.90 [0.2-115.1] vs. 1.56 [0.1-1367.6], respectively, P = 0.005). CONCLUSIONS: In type 2 diabetic patients, increased UAE is strongly associated with insulin resistance and related cardiovascular risk factors. This association seems to be stronger in men than in women.

Serum thyroglobulin and 131I whole body scan after recombinant human TSH stimulation in the follow-up of low-risk patients with differentiated thyroid cancer.

OBJECTIVE: The 'standard' postoperative follow-up of patients with differentiated thyroid cancer (DTC) has been based upon serum thyroglobulin (Tg) measurement and (131)I whole body scan ((131)I-WBS) after thyroid hormone (T(4)) treatment withdrawal. However, (131)I-WBS sensitivity has been reported to be low. Thyroid hormone withdrawal, often associated with hypothyroidism-related side effects, may now be replaced by recombinant human thyroid stimulating hormone (rhTSH). The aim of our study was to evaluate the diagnostic accuracy of (131)I-WBS and serum Tg measurement obtained after rhTSH stimulation and of neck ultrasonography in the first follow-up of DTC patients. DESIGN: Ninety-nine consecutive patients previously treated with total thyroidectomy and (131)I ablation, with no uptake outside the thyroid bed on the post-ablative (131)I-WBS (low-risk patients) were enrolled. METHODS: Measurement of serum Tg and (131)I-WBS after rhTSH stimulation, and ultrasound examination (US) of the neck. RESULTS: rhTSH-stimulated Tg was 1 ng/ml (Tg+) in 21 patients, including 6 patients with Tg levels >5 ng/ml. (131)I-WBS was negative for persistent or recurrent disease in all patients (i.e. sensitivity = 0%). US identified lymph-node metastases (confirmed at surgery) in 4/6 (67%) patients with stimulated Tg levels >5 ng/ml, in 2/15 (13%) with Tg >1<5 ng/ml, and in 2/78 (3%) who were Tg-negative. CONCLUSIONS: (i) diagnostic (131)I-WBS performed after rhTSH stimulation is useless in the first follow-up of DTC patients; (ii) US may identify lymph node metastases even in patients with low or undetectable serum Tg levels.

Combined 17alpha-Hydroxylase/17,20-lyase deficiency caused by Phe93Cys mutation in the CYP17 gene.

Seventeen alpha-hydroxylase/17,20-lyase deficiency is a rare, autosomal recessive form of congenital adrenal hyperplasia not linked to human leukocyte antigen and characterized by the coexistence of hypertension caused by the hyperproduction of mineralocorticoid precursors and sexual abnormalities, such as male pseudohermaphroditism and sexual infantilism in female, due to impaired production of sex hormones. Both 17alpha-hydroxylase and 17,20-lyase reactions are catalyzed by a single polypeptide, cytochrome P450c17 (CYP17), which is encoded by the CYP17 gene located on chromosome 10q24-q25. Mutations in the CYP17 gene have been recognized to cause the 17alpha-hydroxylase/17,20-lyase deficiency syndrome. Here, we describe two phenotypically and hormonally affected Italian patients with 17alpha-hydroxylase/17,20-lyase deficiency. The family history revealed consanguinity of the parents. Linkage and haplotype analyses using microsatellites on chromosome 10q24-q25 demonstrated that the two affected individuals were homozygous at these loci. The mutation screening of the CYP17 gene identified a new Phe93Cys missense mutation in exon 1. The amino acid substitution is located in a highly conserved region of the protein and is not a polymorphism because it is not present in one hundred normal alleles. In vitro functional studies showed that the Phe93Cys mutated CYP17 retains only 10% of both 17alphahydroxylase and 17,20-lyase activities, according to the severe phenotype. Our results shed more light on the structure-function relationship of the CYP17 protein indicating that Phe 93 is crucial for both enzymatic activities.