Reference Values for TSH and Free Thyroid Hormones in Healthy Pregnant Women in Poland: A Prospective, Multicenter Study.

OBJECTIVES: The diagnosis and treatment of thyroid diseases in pregnant women remains a challenge. Various medical associations recommend establishing the reference intervals for thyroid hormones by a local laboratory. Considering differences within geophysical, socioeconomic conditions, and iodine prophylaxis in various populations, it is advisable to assess reference intervals for thyroid hormones specific to a region of residence. The objective was to assess trimester-specific reference intervals for TSH, fT3, and fT4 for pregnant women in the Polish population. METHODS AND RESULTS: We conducted a prospective study in 4 centers representing different regions of Poland (Krakow, Warsaw, Poznan, and Bialystok). Our study included consecutive, healthy pregnant women (172 patients), with an age range of 27-47 years. All women had a negative history for thyroid diseases, normal thyroid peroxidase antibody levels, and proper iodine prophylaxis. All newborns had TSH levels in the appropriate reference range. Serum TSH, fT3, fT4, and thyroid-peroxidase antibodies were measured in each trimester. The reference intervals were calculated using the percentile method, as recommended by the International Federation of Clinical Chemistry. The reference values calculated were 0.009-3.177, 0.05-3.442, and 0.11-3.53 mIU/L for TSH; 3.63-6.55, 3.29-5.45, and 3.1-5.37 pmol/L for fT3; and 11.99-21.89, 10.46-16.67, and 8.96-17.23 pmol/L for fT4 in consecutive trimesters of pregnancy. Reference intervals for pregnant women when compared to the general population showed a lower concentration of TSH in every trimester of pregnancy and lower fT4 in the 2nd and 3rd trimesters. CONCLUSIONS: Using appropriate trimester-specific reference intervals may improve care of pregnant women by preventing misdiagnosis and inadequate treatment.

Amiodarone and the thyroid.

Amiodarone, a benzofuranic iodine-rich antiarrhythmic drug, causes thyroid dysfunction in 15-20% of cases. Amiodarone can cause both hypothyroidism (AIH, amiodarone-induced hypothyroidism) and thyrotoxicosis (AIT, amiodarone-induced thyrotoxicosis). AIH is treated by L-thyroxin replacement and does not need amiodarone discontinuation. There are two main forms of AIT: type 1, a form of true iodine-induced hyperthyroidism; and type 2, a drug-induced destructive thyroiditis. However, mixed/indefinite forms exist, contributed to by both pathogenic mechanisms. Type 1 AIT usually occurs in diseased thyroid glands, whereas type 2 AIT develops in substantially normal thyroid glands. Thioamides represent the first-line treatment for type 1 AIT, but iodine-replete glands are poorly responsive; sodium/potassium perchlorate, by inhibiting thyroidal iodine uptake, may increase the response to thioamides. Type 2 AIT is best treated by oral glucocorticoids. Response depends on thyroid volume and severity of thyrotoxicosis. Mixed/indefinite forms may require a combination of thioamides, potassium perchlorate, and steroids. Radioiodine treatment is usually not feasible because amiodarone-related iodine load decreases thyroidal radioiodine uptake. Thyroidectomy represents an important and helpful option in cases resistant to medical therapy. Surgery performed by a skilled surgeon may represent an emergent treatment in patients who have severe cardiac dysfunction.

Dietary patterns as risk factors of differentiated thyroid carcinoma.

UNLABELLED: Nutritional factors are known to be important in the development of different metabolic diseases. The history of nodular or diffuse goiter is closely related to risk of thyroid carcinoma. On account of the function of the thyroid gland, many studies focus on iodine intake. The aim of the study was to assess whether dietary patterns could be risk factors of differentiated thyroid carcinoma. MATERIAL/METHODS: The case-control study was based on a questionnaire, which included information about dietary patterns and was carried out on 284 patients comprising 30 males (mean age 58.4±13.7 years), and 254 females (mean age 52.1±13.8 years), as well as 345 randomly selected controls: 58 males (mean age 60.2±12 years) and 287 females (mean age 53.4±14.3 years) randomly selected from the Population Register and adjusted by age and gender to the group of TC. The main groups of nutritional products, i.e. starchy foods, meat, dairy products, vegetables, fruits, and beverages, were analyzed. RESULTS: Consumption of vegetables, fruits, saltwater fish and cottage cheese was significantly lower in patients with differentiated thyroid carcinoma than in controls, quite the contrary to starchy foods, especially white bread. CONCLUSIONS: Dietary patterns appear to modify the risk of thyroid carcinoma. A diet rich in vegetables and fruit, as well as saltwater fish (a source of iodine) and low-fat meat, could be an important protective factor.

[Management of thyroid diseases during pregnancy]. / Postepowanie w chorobach tarczycy u kobiet w ciazy.

The management of thyroid disorders during pregnancy is one of the most frequently disputed problems in modern endocrinology. It is widely known that thyroid dysfunction may result in subfertility, and, if inadequately treated during pregnancy, may cause obstetrical complications and influence fetal development. The 2007 Endocrine Society Practice Guideline endorsed with the participation of the Latino America Thyroid Association, the American Thyroid Association, the Asia and Oceania Thyroid Association and the European Thyroid Association, greatly contributed towards uniformity of the management of thyroid disorders during pregnancy and postpartum. Despite the tremendous progress in knowledge on the mutual influence of pregnancy and thyroid in health and disease, there are still important areas of uncertainty. There have been at least a few important studies published in the last 3 years, which influenced the thyroidal care of the expecting mother. It should also be remembered that guidelines may not always be universally applied in all populations with different ethnical, socio-economical, nutritional (including iodine intake) background or exposed to different iodine prophylaxis models. The Task Force for development of guidelines for thyroid dysfunction management in pregnant women was established in 2008. The expert group has recognized the following tasks: development of the coherent model of the management of thyroid dysfunction in pregnant women, identification of the group of women at risk of thyroid dysfunction, who may require endocrine care in the preconception period, during pregnancy and postpartum - that is in other words, the development of Polish recommendations for targeted thyroid disorder case finding during pregnancy, and the development of Polish trimester-specific reference values of thyroid hormones. Comprehensive Polish guidelines developed by the Task Force are to systematize the management of the thyroid disorders in pregnant women in Poland.

[Assessement of the usefulness of whole body scintigraphy after administration of 6 MBq of 131I in the diagnostic of breast cancer]. / Ocena mozliwosci zastosowania scyntygrafii calego ciala po podaniu 6 MBq 131I w diagnostyce raka sutka.

INTRODUCTION: Sodium-iodine symporter (NIS) belongs to a large family of natrium dependent ion transporters found in normal thyroid cells located on the basilar membrane of tyreocytes. Under physiologic conditions, the NIS is also present in other tissues: salivary glands, gastric mucosa, mammary glands during lactation, and vascular plexus of the fourth ventricle. NIS expression has also been found in many tumors, including breast cancer. AIM: The aim of this study was to evaluate the usefulness of whole body scintigraphy after administration of relatively low activity of 131I (6 MBq)in the diagnostics of breast cancer. MATERIAL AND METHODS: The study included nine women with breast cancer, aged 38-73 years (mean 55.6 +/- 11.7 years) and a control group of 14 women aged 29-84 years (mean 48.8 +/- 16.7 years). The uptake of radioiodine in whole body scintigraphy 24 hours after administration of 131I radioiodine (6 MBq) was compared between the control group and breast cancer patients. No pharmaceuticals reducing thyroid iodine uptake or increasing NIS expression were used. RESULTS: Whole body scans using 6 MBq 131I activity revealed no focal radioiodine uptake outside the thyroid tissue in patients with breast cancer as well as volunteers from the control group. CONCLUSIONS: Whole body scintigraphy using 131I, dosed at 6 MBq, with no additional treatment increasing extrathyroidal uptake of radioiodine, appears to be ineffective in the imaging of breast cancer.

Adenomatoid tumour of the adrenal gland: a case report and literature review.

Adenomatoid tumour (AT) is a rare, benign neoplasm of mesothelial origin, which usually occurs in the genital tract of both sexes. Occasionally these tumours are found in extra genital locations such as heart, pancreas, skin, pleura, omentum, lymph nodes, retroperitoneum, intestinal mesentery and adrenal gland. Histologically ATs show a mixture of solid and cystic patterns usually with focal presence of signet-ring like cells and scattered lymphoid infiltration. The most important thing about these tumours is not to mis-diagnose them as primary malignant or metastatic neoplasms. We present a case of an adrenal AT in a 29-year-old asymptomatic male. The tumour was an incidental finding during abdominal CT-scan for an unrelated condition. We also present a review of the literature concerning adrenal gland AT and give possible differential diagnosis.

[Diagnostic difficulties in recognizing of pheochromocytoma]. / Trudnosci diagnostyczne w rozpoznawaniu guza chromochlonnego nadnercza.

Pheochromocytoma (PH) is a tumour of chromaffin cells of the sympathetic nervous system and its clinical symptoms are associated with excessive production and release of catecholamines. The main criterion for clinical diagnosis of PH is finding increased concentrations of catecholamines or their metabolites in serum and/or urine. The largest diagnostic and therapeutic problems are patients with slightly elevated levels of methoxycatecholamines in serum and/ or urine. Aim of this study was to determine the cut-off point for elevated methoxycatecholamine in the collection of daily urine, which would give the basis for determining the reasonable recommendations of the biochemical criteria for diagnosis of PH. Retrospectively we analysed the results of 45 patients sent to laparoscopic adrenalectomy to the Department of General Surgery II with the preoperative diagnosis of pheochromocytoma. The diagnosis of pheochromocytoma was based on the finding of elevated 24-hour urine methoxycatecholamines. Based on the results of the histopathological examination patients were divided into two groups. Group 1 included 27 patients (14 women and 13 men) with histopathologically confirmed pheochromocytoma of adrenal gland. Group 2 consisted of 18 patients (11 women and 7 men), in which histopathological examination did not confirm the presence of pheochromocytoma. Mean age of patients in group 1: 46.8 +/- 14.4 years, in group 2: 55.7 +/- 13.7 years. Hypertension was diagnosed in 77.8% of those with group 1 and 94.4% from group 2. Based on the analyzed results of the CT, we found that the average tumor size in group 1 (4.2 +/- 1.9 cm) was statistically higher than in group 2 (2.9 +/- 1.1 cm). The average concentration of normetanephrine (NMN) in 24-hour urine in group 1 was statistically significantly higher than in group 2 (2,686 +/- 870.4 vs. 2375.1 +/- 754 mg/24h), as well as the average concentration of metanephrine (MN) (2533.4 +/- 3269.3 +/- 491.6 vs. 371.5 mg/24 hrs), and the sum of both methoxycatecholamines (NMN + MN) (5219.3 +/- 5190.6 vs. 1241.8 +/- 1202.2). The highest sensitivity in diagnosing pheochromocytoma with the rate of 81.5% was obtained for the sum of normetanephrine and metanephrine in 24-hour urine, while the sensivity for levels of each methoxycatecholamine separately was similar (63%). The highest specificity in the exclusion of PH was shown for 24-hour urine metanephrine (94.4%). The highest positive predictive value was found for the level of metanephrine in 24-hour urine (94.4%). The diagnostic cutoff concentrations of NMN, MN and NMN + MN for the diagnosis of pheochromocytoma were set. For the 24-hour urine NMN- cut-off > 1500 ug/24 h, for MN > 700 ug/24h and for NMN + MN > 1350 ug/24h. Shown above cut-off levels of methoxycatecholamines urine concentration will allow to pose a more accurate preoperative diagnosis of PH.

[Disseminated adrenocortical carcinoma: case report]. / Rozsiany rak kory nadnercza.

Adrenocortical carcinoma is a rare neoplasm occurring with a frequency of 1-2 cases per million. It is characterized by significant malignancy with mean survival of about 28 months, and in the presence of documented metastases survival is shorter up to 8 months. This type of a tumor is slightly more frequent in women (58.6%) than in men (41.4%). Etiology of adrenocortical carcinoma is still unclear, but a role of genetic and environmental factors has been largely considered. Most of the carcinomas (60%) are functional and usually the first manifestation is Cushing's syndrome with virilization. The tumor size is still the best single predictor of prognosis. Histopathology specimen from biopsy or obtained during operation should be stained for Melan A, which can confirm the adrenal origin of the tumor. The only method of treatment is a complete surgical excision of the carcinoma. However, because of its dynamics, metastases cannot be reliably excluded. We presented the case of functioning adrenocortical cancer in 37-year-old patient who at time of diagnosis had 12 cm in diameter tumor of the left adrenal gland and metastases to the liver and lung. In the article the symptoms associated with hormones produced by the carcinoma, diagnostics and treatment with regard to the progression of the disease have also been discussed.

[Graves-Basedow disease after allogeneic bone marrow transplantation]. / Choroba Graves-Basedowa u pacjentki po allogenicznym przeszczepie szpiku.

One severe aplastic anaemia case who presented autoimmune thyroid disease after allogeneic bone marrow transplantation (alloBMT) is described. A 19 year old Polish girl developed Graves' hyperthyroidisms 19 months after allogeneic BMT for severe aplastic anaemia (SAA) donated from her brother. Her serum was positive for thyroid stimulating antibody (TSAb) and anti-thyroid peroxidase autoantibodies (aTPO) while her brother remained euthyroid, seronegative for TSAb, and showed no clinical signs of thyroid pathology. The genetic studies of lymphocytes FISH (fluorescence in situ hybridization) and analysis of STR (short tandem repeated) fragments suggested, that lymphocytes responsible for hyperthyroidisms were of donor origin.

Macro- and microadenoma of thyrotropin secreting pituitary tumors--two clinical cases.

Thyrotropin secreting adenoma, thyrotropinoma (TSH-oma), is a rare cause of hyperthyroidism--called secondary hyperthyroidism. The hormonal profile in pituitary hyperthyroidism is characterized by a nonsuppressed TSH in the presence of high levels of free thyroid hormones (fT4, fT3) reflecting an abnormal feedback. The diagnosis of TSH-oma is often made at the stage of macroadenoma because of the aggressive nature of the tumor and due to the fact that patients are mistakenly treated for more common primary hyperthyroidism for a long time. Two cases of TSH-secreting adenoma were detected in Chair and Department of Endocrinology, Collegium Medicum of the Jagiellonian University in Krakow for the last twenty years. Case 1: 49 year old woman was admitted to the Clinic of Endocrinology in 1999 with recurring hyperthyroidism treated with surgical thyroid ablation in 1992 and thyreostatics for the previous nine years. On admission to the Clinic her thyroid panel presented with elevated free hormone levels (mainly fT3-14.8 pmol/l) and not suppressed TSH-0.7 mIU/l suggesting central hyperthyroidism. MRI scan of the pituitary gland revealed microadenoma of 5 mm in diameter. She was qualified to transsphenoidal resection of the tumor. Histopathology revealed acidophilic adenoma with positive TSH staining. Thyroid hormones 8 days after the operation suggested full effectiveness of the surgery. Case 2: 65 year old man treated for one year with L-Thyroxin because of elevated TSH (60 mIU/l) and then with thyreostatics for elevated fT3 and fT4 was admitted to the Clinic of Endocrinology in 2000 with suspected thyrotropinoma. On admission to the Clinic thyroid panel suggested hyperthyroidism with fT4-40 pmol/l, FT3-11.2 pmol/l without suppression of TSH 2.2 mIU/l. MRI scan revealed a pituitary tumor 20 x 18 x 20 mm, compressing the optic chiasm. He was administered octreotide as a preparation for the operation. The patient underwent trans-sphenoidal resection of the adenoma (histopathologically a chromophobic adenoma). The example of presented patients suggests that clinical course of the pituitary tumor producing TSH and the rate of the tumor growth may differ significantly. Surgical resection of TSH producing adenoma is the most effective therapy. It should be proceeded by octreotide administration in patients with macroadenoma.