Recombinant human thyrotropin versus thyroid hormone withdrawal in differentiated thyroid carcinoma follow-up: a single center experience.

Introduction: Our goal was to evaluate and compare the diagnostic utility of thyroid hormone withdrawal (THW) and recombinant thyroid-stimulating hormone (rhTSH) methods in detecting recurrence/persistence (R/PD) of differentiated thyroid carcinoma (DTC). Methods: The study included 413 patients with DTC who underwent total thyroidectomy and had remnant ablation. DxWBS, s-Tg levels, R/PD were evaluated retrospectively. A s-Tg level≥2 ng/mL was considered as "positive s-Tg". Results: DxWBS and s-Tg levels were evaluated with rhTSH in 116 and THW in 297 subjects, respectively. The sensitivity and specificity of "positive s-Tg" for R/PD in THW group were 77.3% and 92.7%, with 90.3% accuracy, respectively. The sensitivity and specificity of "positive s-Tg" for R/PD in rhTSH group were 58.8% and 100% with 93.9 % accuracy, respectively. An uptake outside thyroid bed at WBS showed a sensitivity of 17.1%, specificity of 100% for R/PD with 89.4% accuracy in THW group. An uptake outside thyroid bed at WBS showed a sensitivity of 7.7%, specificity of 100% for R/PD with 88.8% accuracy in rhTSH group. Conclusion: Method of TSH stimulation did not influence the reliability of DxWBS. The "positive s-Tg level" had a higher sensitivity with THW when compared to rhTSH in detecting R/PD.

THE ASSOCIATION BETWEEN LYMPH NODE METASTASIS AND MOLECULAR MARKERS IN DIFFERENTIATED THYROID CANCER.

CONTEXT: There is no consensus regarding routine usage and benefits of molecular markers for prediction of prognosis and assessment of risk groups in differentiated thyroid cancer (DTC). OBJECTIVE: We aimed to investigate NIS, Galectin-3, PTEN, P53 and Ki67 expressions in tumor tissue and metastatic lymph nodes in PTC and their association with lymph node metastasis and prognosis. MATERIAL AND METHODS: Ninety two papillary thyroid cancer patients who underwent total thyroidectomy and central lymph node dissection were included in this study. NIS, Galectin-3, PTEN, P53 and Ki67 immunohistochemical stainings were performed for all surgical tumor tissues and metastatic lymph nodes of the 38 patients. Age, gender, tumor size, multifocality, capsular invasion, extrathyroidal extension and lymphocytic thyroiditis were assessed retrospectively. RESULTS: Seventy three females (79.3%) and nineteen males (20.7%) were included in this study. Risk of lymph node metastasis was higher in tumors with capsular invasion and extrathyroidal extension (p=0.03 and p < 0.001). NIS, PTEN and Galectin-3 protein expressions in tumor tissue were not associated with gender, tumor size, multifocality, extrathyroidal extension, capsular invasion, lymph node metastasis and tumor recurrence. Mean Ki 67 proliferation index was 2.08±0.95%. Ki 67 proliferation index was associated with tumor size (p=0.012). Intensity and expression of NIS and PTEN in tumor tissue were concordant with intensity and expression in metastatic lymph nodes (p<0.001). Ki 67 proliferation index in tumor was concordant with metastatic lymph nodes (p=0.02). CONCLUSIONS: NIS, PTEN, Galectin-3, Ki67 and P53 expressions were not associated with the risk of lymph node metastasis in PTC patients. Routine analysis of these markers does not seem to be favorable. Further studies with new markers are necessary to determine prognostic predictors.

Multiple endocrine neoplasia type 2A/localized cutaneous lichen amyloidosis associated with malignant pheochromocytoma and ganglioneuroma.

We hereby present a rare variant of multiple endocrine neoplasia type 2A (MEN2A) associated with a rare skin disease primary cutaneous lichen amyloidosis and discrete malignant pheochromocytoma in both adrenal glands and pancreatic tail, and interestingly accompanied ganglioneuroma located in retroperitoneum in a 34-yr-old female. The presence of composite tumor of pheochromocytoma and ganglioneuroma arising in the adrenal glands has been described previously in MEN2A and in sporadic cases. The patient displayed classical signs and symptoms of catecholamine excess. Biochemical screening proved pheochromocytoma. Computed tomography revealed multiple mass lesions in both adrenal glands. It also showed a large heterogeneous mass that clearly discriminated from right adrenal gland in retroperitoneal location. After surgical exploration, both adrenal glands and the suspicious mass in pancreatic tail were removed successfully together with subtotal resection of the retroperitoneal tumor. Histopathologic examinations confirmed the presence of pheochromocytoma in both adrenal glands as well as pancreatic lesion. A retroperitoneal ganglioneuroma was also present. Symptomatic and biochemical evidence of pheochromocytoma subsided after the operation. Further evaluation for medullary thyroid carcinoma and primary hyperparathyroidism confirmed MEN2A. Mutation analysis of the ret proto-oncogene revealed a missense point mutation at position 634 in exon 11, which gives rise to the substitution of a cysteine codon with a tyrosine residue.

Role of ovary and adrenal glands in hyperandrogenemia in patients with polycystic ovary syndrome.

Ovary is the main source of the hyperandrogenism in polycystic ovary syndrome (PCOS). Adrenal glands may also be involved in the pathogenesis of the development of PCOS. To investigate this possibility and to find out if buserelin test is able to distinguish PCOS patients from the patients with idiopathic hirsutism (IH), ACTH and buserelin tests were performed in 29 women with PCOS, 21 women with IH, and 20 control subjects (CS). We also aimed to determine the role of dysregulation of 17 hydroxylase in the development of PCOS. Basal and stimulated dehydroepiandrosterone sulfate (DHEA-S) and stimulated cortisol (F) levels after ACTH administration were significantly higher in PCOS group than in IH and CS groups (p<0.0001 and p<0.05, respectively). PCOS patients also possessed significantly higher basal and stimulated 17-hydroxyprogesterone (17-OH P) levels, including the peak levels (p<0.02), during buserelin testing when compared with IH patients and CS. There was no significant correlation between the ACTH-stimulated and the buserelin-stimulated peak 17-OH P values. In conclusion, significantly higher basal and ACTH-stimulated levels of F and DHEA-S in PCOS compared with controls and patients with IH, reflect that adrenal hyperactivity also plays a role in hyperandrogenemia seen in PCOS. Because of the lack of the correlation between ACTH-stimulated and buserelin-stimulated 17-OH P levels, it is hard to say that adrenal hyperactivity seen in PCOS is the result of the dysregulation of cytochrome P450c17-alpha enzyme. Our results suggest that buserelin test which is an GnRH analogue could distinguish at least some of the patients with PCOS from the other patients presenting with the common symptoms of hyperandrogenemia.

Diagnostic value of prostatic specific antigen in hirsute women.

Determination of prostatic specific antigen (PSA) in female tissues has become available recently. The expression of PSA gene is under androgenic regulation. Therefore, hyperandrogenemic states, such as polycystic ovary syndrome (PCOS), are expected to be presented with the higher levels of PSA. The current study aimed at evaluating PSA levels in hirsute women presumed to have PCOS or idiopatic hirsutism (IH). Thirty-three patients with PCOS, 40 patients with IH, and 20 healthy control subjects were enrolled in the study. Beside basal hormonal evaluation, total PSA (tPSA), and free PSA (fPSA) were determined in all subjects. Average level of tPSA was the highest in PCOS patients (0.099+/-0.267 ng/ml) when compared with IH and control subjects (p<0.05 and p<0.001, respectively). Besides, mean fPSA levels were found to be significantly higher in patients with PCOS than healthy controls (0.033+/-0.070 vs 0.010+/-0.001 ng/ml; p<0.05). Both total and free PSA levels were found to be higher in 73 hirsute women than in control subjects (p<0.01 and p<0.05, respectively). Women with hyperandrogenemia tended to have higher tPSA than women without hyperandrogenemia (p<0.01). PSA is likely to be used to discriminate hyperandrogenemic hirsutism. If more sensitive assays become available, PSA might be used as a diagnostic criteria for hirsutism and even for some diseases which have hirsutism as a component.

Lymphocytic hypophysitis and infundibuloneurohypophysitis; clinical and pathological evaluations.

This report describes the clinical and pathological characteristics of two patients with lymphocytic hypophysitis (LHy) and two with infundibuloneurohypophysitis (INHy). Two of the patients were women and two were men, and their ages were between 27 and 38 years old. This disease was not associated with either pregnancy or the postpartum period in the female patients. Two of the patients presented with diabetes insipidus, one with panhypopituitarism and right abducens paralysis and one with headache and galactorrhea. At presentation three of the patients had mild to moderate hyperprolactinemia and one had low prolactin levels. All four had abnormal magnetic resonance imaging (MRI): focal nodular enlarging of the infundibulum and normal hypophysis in one, expanding sellar masses in two, and diffusely thickened stalk with slightly enlarged pituitary gland in one. Three cases showed no sign of adenohypophysial deficiency with stimulation tests. One patient had associated chronic lymphocytic thyroiditis. Of the first three patients, one patient underwent transcranial and two underwent transnasal transsphenoidal (TNTS) surgery for mass excisions since they were thought to have pituitary tumors. Endoscopic endonasal transsphenoidal biopsy was performed in the last one with a suspicion of LHy. The pathological and immunohistochemical examinations revealed lymphocytic infiltration. Hyperprolactinemia resolved with surgery in two patients and one developed diabetes insipidus as a complication. We conclude that LHy and infundibuloneurohypophysitis should be considered in the differential diagnosis of the mass lesions of the sellar region and also should be kept in the mind for the etiopathogenesis of cases of hyperprolactinemia, galactorrhea and diabetes insipidus. In suspected cases endoscopic endonasal biopsy for the histopathological diagnosis can be a safe approach.

Degree of thyrotropin suppression in differentiated thyroid cancer without recurrence or metastases.

Forty-eight patients with differentiated thyroid cancer (DTC), who had no evidence of tumor recurrence or metastases on studies such as radioiodine scanning, neck ultrasonography, and with thyrotropin (TSH) and thyroglobulin (Tg) levels less than 1 mU/L and 5 ng/mL, respectively, were included in the study. The mean age was 43 +/- 12 years (range 15-65) and all were receiving levothyroxine (LT4) treatment with a mean dose of 184 +/- 46 microg daily. Patients were divided into two groups; group A included patients that had baseline TSH levels of 0.4 mU/L or more, and group B patients had baseline TSH levels of less than 0.4 mU/L. LT4 doses for all patients were increased, and serum TSH and Tg measurements were reevaluated after 2 months of dose increments. The mean TSH of group A (patients with baseline TSH levels > or = 0.4 mU/L) decreased from 0.67 +/- 0.28 mU/L to 0.16 +/- 0.08 mU/L (p < 0.001), but mean serum Tg level showed no change after dose increments (2.92 +/- 1.36 ng/mL vs. 3.59 +/- 0.93 ng/mL at the second month; p > 0.05). Similar results were also observed in group B (patients with baseline TSH levels < 0.4 mU/L). Mean TSH level decreased from 0.26 +/- 0.07 mU/L to 0.1 +/- 0.05 mU/L (p = 0.006), but no decrease occurred in mean Tg level (3.0 +/- 1.16 ng/mL vs. 3.3 +/- 1.03 ng/mL; p > 0.05). The patients' data were reevaluated according to second-month TSH levels. Patients with a TSH level between 0.11 to 0.4 mU/L were set as "final TSH > 0.1 group," and patients with a TSH level equal or less than 0.1 mU/L were set as "final TSH < or = 0.1 group," and baseline and second-month Tg levels were assessed. The mean second month Tg levels did not differ in these two patient groups (3.7 +/- 0.74 ng/mL for final TSH > 0.1 group vs. 3.3 +/- 1.2 ng/mL for final TSH < or = 0.1 group; p > 0.05). No difference could be found between initial and second-month Tg levels in both groups (2.8 +/- 1.4 ng/mL vs. 3.7 +/- 0.74 ng/mL in final TSH > 0.1 group and 3.11 +/- 1.1 ng/mL vs. 3.3 +/- 1.2 in final TSH < or = 0.1 group; p > 0.05). In conclusion, these results indicate that serum Tg levels cannot be suppressed by maximal TSH suppression in tumor-free DTC patients. The suppression of TSH to less than 0.1 mU/L seems not to be necessary in most patients who have no evidence of active disease.

Lymphocytic infundibuloneurohypophysitis presenting as diabetes insipidus in a man.

We report a patient with diabetes insipidus, whose sella magnetic resonance imaging revealed a normal hypophysis with a focal nodular thickening of the infundibulum and lack of hyper-intense signal of the normal neurohypophysis. The histopathologic examination of the lesion showed a lymphoplasmacytic, predominantly lymphocytic, infiltration. A diagnosis of lymphocytic infundibuloneurohypophysitis was made, by the exclusion of other infiltrative, granulomatous diseases.

A potential risk for osteomalacia due to sociocultural lifestyle in Turkish women.

Osteomalacia is a metabolic bone disease caused by deficiency of vitamin D or its active metabolites. Because poor sunlight exposure is one of the most common causes of osteomalacia, the disease seems to be rare in countries with adequate sunlight. We report nine Turkish female patients with osteomalacia with ages between 21 and 50 years. Osteomalacia was diagnosed on the basis of a history of bone aches or pains, muscle weakness, low or low normal serum calcium and urinary calcium, decreased concentrations of serum inorganic phosphorus and 25- hydroxyvitamin D and increased serum intact PTH and alkaline phosphatase levels. Radiographically, pseudo-fractures were present in seven of the patients. The patients' symptoms and signs were relieved with the treatment with vitamin D analogues and calcium. Their hypovitaminosis D are suggested to be caused by excessive clothing in the outdoors due to sociocultural and religious reasons. Excessive clothing may be a risk factor for osteomalacia in young to middle-aged and otherwise healthy women even in countries with adequate sunlight.

Omeprazole: calcitonin stimulation test for the diagnosis follow-up and family screening in medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) occurs sporadically but may also be inherited as part of the multiple endocrine neoplasia (MEN) type 2 syndrome. Screening of the patients and first degree relatives annually with basal and provocative tests for serum immunoreactive calcitonin (CT) levels is essential and enables potentially curative disease. Pentagastrin and calcium are the usual provocative agents used worldwide. We used endogenous gastrin (GT) release achieved by omeprazole, 20 mg b.i.d., to stimulate CT in 9 MTC, in 3 MEN 2A family members, and in 50 healthy control subjects. A steady and significant increase both in GT and CT levels was achieved in 9 MTC patients and 3 of the 14 family members tested, whereas in healthy controls the CT increase stimulated by GT was insignificant. Preliminary results showed that this new, safe, cheap, and outpatient-basis test can be used in MTC diagnosis, follow-up, and screening.

Non-Hodgkin's lymphoma presenting as thyroid and adrenal gland involvement.

We report an unusual case of non-Hodgkin's lymphoma involving both the thyroid and adrenal glands. Malignant infiltration of the glands by B-cell immunoblastic type lymphoma were demonstrated by cytologic findings in needle biopsy. Staging studies showed minor nodal involvement. The patient was treated with combination chemotherapy. Simultaneous involvement of the thyroid and adrenal glands with non-Hodgkin's lymphoma is very rare. In this report, while presenting this rare coexistence, we also want to emphasize that fine-needle aspiration biopsy was useful in the diagnosis.