The hypothalamic-pituitary-adrenal axis in women with differentiated thyroid cancer.

INTRODUCTION: We studied the function of hypothalamic-pituitary-adrenal (HPA) axis in females with differentiated thyroid cancer (DTC) and its sequelae on metabolism and cardiovascular risk. METHODS AND RESULTS: Sixteen women were investigated with (1) morning, evening, and midnight cortisol and adrenocortophic hormone, (2) cortisol after overnight 1 mg dexamethasone suppression test, (3) cortisol after corticotropin releasing hormone test, (4) oral glucose tolerance test with glucose and insulin estimations, and (5) ultrasound for carotid intima media thickness. A matched control group underwent similar investigations. None of the parameters was significantly different between patients and controls. CONCLUSION: Females with DTC have normal HPA-axis function and similar insulin sensitivity and cardiovascular risk compared to controls.

Cervical masses as manifestation of papillary thyroid carcinomas

BACKGROUND: Papillary thyroid microcarcinomas are tumors often found accidentally after thyroidectomy for other thyroid disorders. METHODS: Patients with enlarged lateral cervical masses, with unknown thyroid disease, found to have metastases from papillary thyroid carcinoma

Mortality from thyroid cancer in patients with hyperthyroidism: the Theagenion Cancer Hospital experience.

BACKGROUND: Thyroid carcinoma has been reported in patients operated for different types of hyperthyroidism and the probability of a hot nodule being malignant seems to be low. The aim of the present study was to explore the relationship between thyroid cancer, hyperthyroidism and outcome in a large cohort of patients who presented to a tertiary cancer centre in Northern Greece. PATIENTS: Among 720 patients treated for thyroid cancer, 60 had a concomitant diagnosis of hyperthyroidism due to Graves' disease (n=14), solitary autonomous adenoma (n=17), or multinodular goiter (n=29). Adverse prognostic factors were common in patients with a previous history of hyperthyroidism at the time of diagnosis of thyroid cancer, including cases where the cancer was discovered coincidentally after thyroid surgery for hyperthyroidism and cases where tumor size was more than 10 mm. RESULTS: In 10 out of 17 patients with hyperthyroidism due to solitary autonomous adenomas, the tumor was located within the hot nodule and two of these patients developed local and distant metastases and died from the disease 4 and 15 years after thyroidectomy. CONCLUSION: Clinicians managing patients with hyperthyroidism need to be aware of the possible increased risk of thyroid cancer in this patient group.

Ectopic Cushing's syndrome due to CRH secreting liver metastasis in a patient with medullary thyroid carcinoma.

Ectopic production of CRH by a medullary thyroid carcinoma or its metastases is a rare cause of ectopic Cushing's syndrome (ECS). We report a 45-year old male with medullary thyroid carcinoma (MTC), who, 24 years following the initial diagnosis, presented with clinical and biochemical evidence of an ACTH dependent Cushing's syndrome. Rapid deterioration of his clinical condition and elevated cortisol levels were observed. Computed tomographic imaging of the abdomen revealed extensive liver metastases. The patient underwent fine needle aspiration biopsy of a liver lesion and immunohistochemistry showed that the cells expressed calcitonin, carcino-embryonic antigen and synaptophysin. Further analysis revealed that the material also expressed CRH. This is an unusual case of a CRH-secreting liver metastasis from a medullary thyroid carcinoma 24 years after the initial diagnosis of MTC.

Growth hormone-binding protein is directly and IGFBP-3 is inversely associated with risk of female breast cancer.

OBJECTIVE: Several components of the GH and IGF systems have been implicated in the development of malignancies. All components of these hormonal systems have never been jointly evaluated in female breast cancer, and previous studies have not examined the role of IGF-binding proteins (IGFBP-4, IGFBP-6) or GH-binding protein (GHBP). DESIGN: Hospital-based case-control study. METHODS: In this sample of primarily postmenopausal women, we obtained serum measures of IGF-I, IGF-II, and binding proteins IGFBP-1, IGFBP-3, IGFBP-4, IGFBP-6, as well as GHBP, insulin, and leptin from 74 breast cancer cases and 76 control subjects. RESULTS: In crude analyses, we found lower age-standardized mean IGF-I, IGFBP-3, IGFBP-4, IGFBP-6, and higher IGFBP-1 and GHBP in breast cancer cases when compared with controls. Multivariate models mutually adjusted for other GH-IGF system components and classical breast cancer risk factors demonstrated an inverse association between IGFBP-3 and risk of breast cancer (odds ratio (OR) = 0.2, P < 0.01) and a direct association between GHBP and disease risk (OR = 3.3, P < 0.01). No significant associations were detected in multivariate analyses among IGF-I, IGF-II or IGFBP-1, IGFBP-4, IGFBP-6 with risk of breast cancer, indicating that these factors may not have effects independent of and/or comparable with IGFBP-3 and GHBP. CONCLUSIONS: These results support a protective role of IGFBP-3 and demonstrate for the first time an increased risk of breast cancer with higher GHBP, after accounting for variation in IGFs, IGFBPs, and classical breast cancer risk factors.

Use of a thin-layer technique in thyroid fine needle aspiration.

OBJECTIVE: To investigate the efficacy of the ThinPrep Processor (Cytyc Corporation, Boxborough, Massachusetts, U.S.A) in fine needle aspiration (FNA) of thyroid gland lesions. STUDY DESIGN: This study included 459 thyroid FNA specimens obtained from patients who came to our endocrinology department with various thyroid disorders over 3 years. The cytologic material was prepared using both the conventional and ThinPrep method in the first 2 years (285 cases), while in the last one only the ThinPrep method was used (1 74 cases). The smears were stained using a modified Papanicolaou procedure and May-Grünwald-Giemsa stain. Immunocytochemistry was performed on thin-layer slides using specific monoclonal antibodies when needed. Thin-layer and direct smear diagnoses were compared with the final cytologic or histologic diagnoses, when available. RESULTS: Our cases included 279 adenomatoid nodules, 15 cases of Hashimoto thyroiditis, 45 follicular neoplasms, 14 Hürthle cell tumors, 58 papillary carcinomas and 1 5 anaplastic carcinomas. Thin-layer preparations showed a trend toward a lower proportion of inadequate specimens and a lower false negative rate. Cytomorphologic features showed some differences between the 2 methods. Colloid was less frequently observed on ThinPrep slides, while nuclear detail and micronucleoli were more easily detected with this technique. Moreover, ThinPrep appeared to be the appropriate method for the use of ancillary techniques in suspicious cases. CONCLUSION: Thin-layer cytology improves the diagnostic accuracy of thyroid FNA and offers the possibility of performing new techniques, such as immunocytochemistry, on the same sample in order to detect malignancy as well as the type and origin of thyroid gland neoplasms.

Efficient testing of the RET gene by DHPLC analysis for MEN 2 syndrome in a cohort of patients.

BACKGROUND: Multiple Endocrine Neoplasia type 2 (MEN 2) is an autosomal dominant inherited syndrome characterized by a strong predisposition for developing endocrine tumors. MEN 2 is caused by germline mutations in the ret proto-oncogene. We investigated the feasibility of using the DHPLC technique in mutation detection of the ret gene in members of MTC families. We compared DHPLC analysis with direct sequencing with regard to sensitivity, reliability, cost and time. MATERIALS AND METHODS: Exons 10 and 11 were amplified with PCR from forty-three samples in seventeen unrelated Greek families and were analyzed for mutations by DHPLC and DNA sequencing. RESULTS: Eight PCR amplicons showed a distinct non-wild-type DHPLC profile. Sequence analysis confirmed different nucleotide variations: six of them were localized in exon 10 and two in exon 11. Mutations were detected in five out of seventeen families tested (29%). CONCLUSION: None of the alterations detected by direct sequencing was missed by DHPLC. We conclude that DHPLC is a fast, sensitive, cost-efficient and reliable method for the scanning of ret germline mutations.

The therapeutic value of SST-A octreotide alone or with adjuvant treatment in patients with advanced medullary thyroid carcinoma and positive (111)In-octreotide scan.

Medullary thyroid carcinoma (MTC) as a neuroendocrine tumour arising from C cells of the thyroid gland secrets hormonal peptides; among them, calcitonine (CT) and carcino-embryonic antigen (CEA). These two peptides are used for the diagnosis and treatment response of MTC cases. In patients with advanced MTC, scintigraphy by [(111)In-DTPA-d-phe1]-octreotide is able to detect somatostatin receptors (SSTR) and thus identify regional lymph nodes and/or distal metastases. In this article, we have studied the use of [(111)In-DTPA-d-phe1]-octreotide in the treatment of patients with advanced MTC, and a positive octreotide scan. Twenty-two patients were studied, 16 with persistent MTC and six with relapsed MTC. All patients' tumours were detected by [(111)In-DTPA-d-phe1]-octreotide-scan to be SSTR positive. All patients were treated with the somatostatin analog (SST-A) octreotide, for 3-21 months. Nine patients were treated only with SST-A (Group A). The remaining 13 patients (Group B) received adjuvant treatment as follows: six patients received chemotherapy (Ch), five patients received both Ch and external radiotherapy (eRT) and two patients received only eRT. Results were as follows: Group B patients as compared to Group A patients had about the same objective and biological response. Patients of Group B had relatively better subjective response (less diarrheas and abdominal cramps) versus Group A patients, although this finding was not significant. Group B patients had a longer mean survival time after treatment as compared to Group A patients: 39 months (with a range of 4-72 months) versus 20 months (with a range of 3-60 months) respectively, (P<0.05). Also Group B patients had longer than Group A patients mean total survival time - measured from the start of the disease: 138 (18-270) versus 97 (13-235) months respectively (P<0.05). Based on the above findings, it is the opinion of the authors that patients with advanced MTC and SSTR tumor expression in vivo as indicated by [(111)In-DTPA-d-phe1]-octreotide scanning, when submitted to treatment with SST-A octreotide and adjuvant Ch and/or eRT treatment may have a better treatment response than if submitted to treatment with SST-A octreotide alone. More cases are being studied by us at the present.

Thyroid carcinoma in children and adolescents: presentation, clinical course, and outcome of therapy in 23 children and adolescents in Northern Greece.

OBJECTIVE: To define clinical presentation, surgical complications, follow-up characteristics, and survival of 23 children and adolescents with thyroid carcinoma. DESIGN: Retrospective analysis of data of 23 children and adolescents with thyroid carcinoma cared for in the Theagenion Cancer Hospital, Thessaloniki. RESULTS: At the time of diagnosis cervical lymph node metastases were present in 18 (78.2%), mediastinal in 2 (8.69%), and pulmonary in 3 patients (13%). Total thyroidectomy was performed in 21 patients, with lymph node dissection in 18 and subtotal thyroidectomy in 2. No significant post-operative complications were observed. Histological examination revealed differentiated thyroid carcinoma (DTC). Tumor was multifocal in 11 (47.8%) and bilateral in 7 subjects (63.6%). Thyroid capsule invasion, vascular invasion, soft tissue involvement, and parathyroid gland invasion was observed in 12 out of 23 patients (52.1%). All patients received thyroxine suppressive therapy and 21 of them additional therapy with radioactive iodine (131I). During follow-up (5.5 years), 6 out of the 23 patients presented new metastases in the cervical and mediastinal lymph nodes, lungs, and bones. At last follow-up, 11 patients (47.8%) had residual disease but all were alive. CONCLUSIONS: Thyroid carcinoma in children and adolescents can be quite aggressive. When a young patient presents thyroid nodule or multinodular goiter or palpable lymph nodes, the existence of thyroid carcinoma must be seriously considered.

Cerebellar metastasis as first metastasis from papillary thyroid carcinoma.

Brain metastasis is an uncommon complication of differentiated thyroid carcinoma. Even more, cerebellar metastases from papillary thyroid carcinoma (PTC) are exceptional. We report a 69-year-old male patient with infiltrative PTC who developed high levels of thyroglobulin (Tg) and deteriorated neurological symptoms four years after the initial diagnosis. Computerized tomography (CT) of the brain demonstrated a cerebellar mass and the patient underwent surgery. Pathology revealed metastasis from PTC. Immunochemistry was positive for Tg. The patient had no other sites of distant metastases. Although PTC has generally a good prognosis, metastases to the cerebellum can occur, even as the first metastatic site, despite the fact that appropriate therapy (surgery, radioactive iodine therapy, TSH suppression therapy, chemotherapy and external radiotherapy) had been given for the primary tumour.

Pituitary metastasis of follicular thyroid carcinoma.

OBJECTIVE: The case of a 60-year-old male patient with follicular thyroid cancer who developed a pituitary mass proved to be a metastasis from thyroid cancer. METHODS: Assessment with whole-body scan, ultrasound, computed tomography and thyroglobulin measurements. RESULTS: Despite surgery and repeated doses of radioiodine, the patient developed diplopia and ptosis of the right eyelid, along with increasing thyroglobulin levels. A pituitary mass was discovered, with no signs of pituitary deficiency. The mass was removed and found to consist of neoplastic cells immunohistochemically positive to thyroglobulin. CONCLUSIONS: Distant metastases may develop in cases of follicular thyroid carcinoma, even after repeated doses of (131)I. Metastatic follicular thyroid carcinoma to the pituitary is a rare entity.

Primary tuberculosis of the thyroid gland: report of three cases.

We report on three cases with rapidly increasing thyroid masses who were referred with the provisional diagnosis of thyroid carcinoma. In the two cases, the diagnosis of tuberculosis was established after thyroidectomy, but in the third case diagnosis was made pre-operatively with acid fast bacilli (AFB) staining and culture from fine needle aspiration (FNA) material. Although rare, tuberculosis of the thyroid gland should be included in the differential diagnosis of thyroid masses. FNA, AFB staining and culture of the aspirate are important diagnostic tools in these cases.