Maria Gryczyńska

A coding variant in NLRP1 is associated with autoimmune Addison's disease.

Autoimmune Addisons disease (AAD) is a complex disorder with several susceptibility loci. Variations in the NLRP1 (previously, NALP1) gene have recently been reported to confer risk for vitiligo and associated autoimmune conditions. We hypothesized that polymorphisms in this gene may affect susceptibility to AAD. The aim of this study was to analyze the associations of six NLRP1 single-nucleotide polymorphisms (SNPs) with AAD within a Polish cohort. The study comprised 101 AAD patients and 254 healthy control individuals. Genotyping was performed by polymerase chain reaction followed by restriction fragment length polymorphism and single strand conformation polymorphism methods. The minor allele of the coding SNP rs12150220 appeared significantly more frequently in AAD compared with healthy individuals (OR = 1.5, 95% CI, 1.08-2.08, p = 0.015). The distribution of genotypes also demonstrated significant differences. The frequency of high-risk genotype AA of rs12150220 SNP was significantly increased among AAD subjects versus controls (p = 0.006 and p = 0.036, respectively; significant after Bonferroni correction), yielding an OR of 2.96 (95% CI, 1.34-6.55). Likewise, the heterozygous genotype TA was observed more frequently in the patient group [OR = 3.09 (95% CI, 1.53-6.24), p = 0.001 and p = 0.006 after Bonferroni correction]. In conclusion, this study confirms an association between the coding polymorphism in NLRP1 and AAD.

The tryptophan 620 allele of the lymphoid tyrosine phosphatase (PTPN22) gene predisposes to autoimmune Addison's disease

Objective  Previous studies of the association between autoimmune Addisons disease (AAD) and a nonsynonymous single nucleotide polymorphism (SNP) in the PTPN22 gene (C1858T, pR620W; SNP ID no. rs2476601) have shown conflicting results. We aimed to examine this association using additional cohorts of AAD subjects from the UK and Poland.

Chromogranin A – unspecific neuroendocrine marker. Clinical utility and potential diagnostic pitfalls

Chromogranin A, despite a number of limitations, is still the most valuable marker of neuroendocrine tumors (NETs). Granins belong to the family of acidic proteins that constitute a major component of secretory granules of various endocrine and neuroendocrine cells, which are components of both the classical endocrine glands and the diffuse neuroendocrine system. These cells are a potential source of transformation into neuroendocrine tumors. The awareness of potential causes influencing the false results of its concentrations simplifies diagnosis and treatment. One of the disadvantages of this marker is its non-specificity and the existence of a number of pathological processes leading to an increase in its concentration, which often results in confusion and diagnostic difficulties. The molecular structure is characterized by a number of sites susceptible to the proteolytic activity of enzymes, resulting in the formation of a number of biologically active peptides. Presumably they act as precursors of active proteins. Chromogranin expression correlates with the amount of secretory vesicles in neuroendocrine cells. The peptide chain during biochemical changes becomes a precursor of biologically active proteins with a wide range of activities. There are a number of commercially available kits for the determination of chromogranin A, which differ in methodology. We present the evaluation of chromogranin A as a marker of neuroendocrine tumors in clinical practice and the possible factors that may affect the outcome of its concentration.

Therapy of large multinodular goitre using repeated doses of radioiodine.

ObjectiveTo evaluate the efficacy of radioiodine therapy using 131I in a group of patients with large multinodular goitre (LMG). MethodsThe study was carried out in patients with goitre volume greater than 100 cm3 and in patients with LMG who were disqualified from surgery. The study included 34 female participants (age range: 62–84 years) with LMG: 26 patients were hyperthyroid and eight patients had a nontoxic goitre. The patients were treated with 800 MBq of radioiodine administered four times at 3-month intervals (total activity of 3.2 GBq). Before each therapy course, serum thyrotropin, free thyroxin, free triiodothyronine and antithyroid antibodies were measured, ultrasonography and thyroid scan were performed. Patients were followed up for a minimum of 24 months. Fine-needle biopsy was done before qualification to the study. ResultsBefore therapy, median thyroid volume was 145 cm3. It decreased during therapy to 65–76 cm3 after 12 months and to 50–62 cm3 after 24 months. After 24 months, 60% of patients were euthyroid and 40% of patients were hypothyroid. During therapy, significant increases in TSHRAb, TPOAb and TgAb levels were observed. No correlation between the levels of antithyroid antibodies, radioiodine uptake, reduction of goitre volume and hormonal status was found. ConclusionIn most cases of LMG, repeated administration of radioiodine is safe and effective. The highest response of the thyroid volume is observed after the first course of treatment. On account of a high incidence of hypothyroidism, the patients should be monitored during and after therapy.

Growth hormone-secreting macroadenoma of the pituitary gland successfully treated with the radiolabeled somatostatin analog (90)Y-DOTATATE: case report.

Pituitary tumors causing acromegaly are usually macroadenomas at the time of diagnosis, and they can grow aggressively, infiltrating surrounding tissues. Difficulty in achieving complete tumor removal at surgery can lead toward a strong tendency for recurrence, making it necessary to consider a means of treatment other than those currently used such as somatostatin analogs (SSAs), growth hormone (GH) receptor antagonist, surgical removal, and radiotherapy. The purpose of this paper is to describe a patient diagnosed with an aggressive, giant GH-secreting tumor refractory to medical therapy but ultimately treated with the radiolabeled somatostatin analog (90)Y-DOTATATE. A 26-year-old male with an invasive macroadenoma of the pituitary gland (5.6 × 2.5 × 3.6 cm) and biochemically confirmed acromegaly underwent 2 partial tumor resections: the first used the transsphenoidal approach and the second used the transcranial method. The patient received SSAs pre- and postoperatively. Because of the progression in pituitary tumor size, he underwent classic irradiation of the tumor (50 Gy). One and a half years later, the patient presented with clinically and biochemically active disease, and the tumor size was still 52 mm in diameter (height). Two neurosurgeons disqualified him from further surgical procedures. After confirming the presence of somatostatin receptors in the pituitary tumor by using (68)Ga-DOTATATE PET/CT, we treated the patient 4 times with an SSA bound with (90)Y-DOTATATE. After this treatment, the patient attained partial biochemical remission and a reduction in the tumor mass for the first time. Treatment with an SSA bound with (90)Y-DOTATATE may be a promising option for some aggressive GH-secreting pituitary adenomas when other methods have failed.

Two diagnoses become one? Rare case report of anorexia nervosa and Cushing’s syndrome

Hypothalamic-pituitary-adrenal axis impairment in anorexia nervosa is marked by hypercortisolemia, and psychiatric disorders occur in the majority of patients with Cushing’s syndrome. Here we report a patient diagnosed with anorexia nervosa who also developed Cushing’s syndrome. A 26-year-old female had been treated for anorexia nervosa since she was 17 years old, and also developed depression and paranoid schizophrenia. She was admitted to the Department of Endocrinology, Metabolism, and Internal Medicine with a preliminary diagnosis of Cushing’s syndrome. Computed tomography revealed a 27 mm left adrenal tumor, and she underwent laparoscopic adrenalectomy. She was admitted to hospital 6 months after this procedure, at which time she did not report any eating or mood disorder. This is a rare case report of a patient with anorexia nervosa in whom Cushing’s syndrome was subsequently diagnosed. Diagnostic difficulties were caused by the signs and symptoms presenting in the course of both disorders, ie, hypercortisolemia, osteoporosis, secondary amenorrhea, striae, hypokalemia, muscle weakness, and depression.

Diagnostic value of selected biochemical markers in the detection of recurrence of medullary thyroid cancer — comparison of calcitonin, procalcitonin, chromogranin A, and carcinoembryonic antigen

INTRODUCTION Medullary thyroid cancer (MTC) is a malignancy of the thyroid gland, which derives from parafollicular C cells. Periodic measurement of biochemical markers of MTC remains a crucial part of patient follow-up and disease monitoring. The aim of the study was to compare the diagnostic value of four selected markers - calcitonin (Ct), procalcitonin (PCT), chromogranin A (CgA), and carcinoembryonic antigen (CEA). MATERIAL AND METHODS Patients with histopathologically confirmed MTC hospitalised in a single department between January 2015 and December 2015 were included in the study. Patients were subdivided into two groups: a remission group and an active disease group, based upon serum markers of MTC and imaging. Levels of Ct, PCT, CgA, and CEA were compared between the groups. RESULTS Forty-four patients were included; 20 patients presented active disease and 24 were in remission. All patients with active disease had Ct exceeding the upper limit of normal range (10 pg/mL) - for that threshold the sensitivity was 100.0% and the specificity was 73.9%; for the best-fit threshold of 121.0 pg/mL the specificity was 95.8% with sensitivity 100.0%. There was significant correlation between Ct and PCT - p < 0.000001, r = 0.93. All patients with active disease exceeded the upper limit of the normal range (0.5 ng/mL) - for that threshold the sensitivity was 100.0% and the specificity was 83.3%; for the best-fit threshold of 0.95 ng/mL the specificity was 95.8% with sensitivity 100.0%. In case of CEA for the best-fit threshold of 12.66 ng/mL the specificity was 100.0% with sensitivity 57.9%; for CgA the best-fit threshold was 75.66 ng/mL with specificity 83.3% and sensitivity 75.0%. CONCLUSIONS Our study confirms that PCT can be considered as an equivalent alternative for measurement of calcitonin. On the other hand, it is also worth noting that MTC can be a rare cause of very high levels of PTC not resulting from infectious diseases. The diagnostic value of CEA and chromogranin A is much lower and can be within the normal range even in patients with advanced, metastatic MTC. They should be used only as accessory markers.

Pyramidal lobe decreases endogenous TSH stimulation without impact on radio-iodine therapy outcome in patients with differentiated thyroid cancer

OBJECTIVES The aim of the study was to assess the frequency of pyramidal lobe (PL) detected in iodine-131 (I-131) scans of thyroid bed in patients after thyroidectomy for differentiated thyroid cancer (DTC) and to investigate influence of PL on endogenous thyrotropin (TSH) stimulation as well as on the effects of the radio-iodine ablation in one-year follow-up. PATIENTS AND METHODS This study was designed as a retrospective analysis of 302 radio-iodine neck scans of patients thyroidectomized due to DTC. The study population was selected from patients with PL detected in thyroid bed scintigraphy. Patients without PL were included to the control group. The study and the control groups did not differ in age, sex of patients, histological type and stage of the DTC. RESULTS Pyramidal lobes were found in 30.5% of all patients. Patients in the study group underwent repeat surgery more often than controls without PL. Preablative TSH level in patients with PL was statistically lower than in the control group, in contrast to free thyroid hormones, which were higher in patients with PL. Preablative and postablative TSH-stimulated thyroglobulin (Tg) and antibodies against thyroglobulin (TgAbs) were measured in both groups, and comparison did not reveal differences. Moreover, for the per-patient analysis, sites of uptake in whole body scintigraphy performed 1 year after radio-iodine remnant ablation (RRA) did not differ between the study and the control groups. CONCLUSION Pyramidal lobe decreases endogenous TSH stimulation without impact on radio-iodine therapy outcome in patients with DTC.

Lack of TSH stimulation in patients with differentiated thyroid cancer - possible causes.

Differentiated thyroid cancer is one of the most common endocrine cancers. Typical standard treatment includes total thyroidectomy with partial lymphadenectomy, then depending on the indications, treatment with iodine isotope 131-I. A prerequisite to conduct the therapy is to obtain endogenic thyroid-stimulating hormone (TSH) stimulation (TSH > 30 µU/ml). We describe two patients with differentiated thyroid carcinoma in whom no rise in serum TSH was observed after withdrawal of thyroxine. In one patient TSH deficiency was due to partial hypopituitarism secondary to a tumor of the pituitary gland. In the second patient the TSH level was suppressed by metabolically active thyroid tissue within bilateral ovarian teratomas. The problems with TSH growth after withdrawal of thyroxine requires additional studies to identify the cause. Above two possible reasons for the lack of TSH stimulation after withdrawal of thyroxine were presented. In the case of non-TSH stimulation due to hypopituitarism both control tests and isotope treatment should be carried out using stimulation by recombinant human TSH (rhTSH).

Cerebellar metastasis of papillary thyroid carcinoma detected with somatostatin receptor scintigraphy

INTRODUCTION Distant metastases of papillary thyroid carcinoma (PTC) may lack the ability to concentrate radioiodine. In such cases, positive somatostatin receptor scintigraphy might be useful in demonstrating the expression of somatostatin receptors that are potential therapeutic targets. To date, only a few cerebellar metastases from PTC have been reported in the literature. PATIENT FINDINGS We present an 82-year-old female, in whom an asymptomatic cerebellar metastasis from PTC was diagnosed by means of Tc-99m-EDDA/HYNIC-TOC scintigraphy four years after the initial diagnosis. She was previously treated with total thyroidectomy and regional lymph node dissection, followed by three cycles of radioiodine therapy. Despite persistently elevated thyroglobulin, no specific radioiodine accumulation was found in the whole body post-treatment scan. Tc-99m-EDDA/HYNIC-TOC scintiscan revealed foci of increased tracer uptake in the lungs, cervical lymph nodes, and a single focus in the head. Thus, therapy with octreotide LAR was initiated. The patient died four months later due to disseminated PTC. SUMMARY In this paper, a patient with asymptomatic previously unknown non-iodine avid cerebellar metastasis of PTC diagnosed by means of scintigraphy using somatostatin analogue Tc-99m-EDDA/HYNIC-TOC is reported. CONCLUSIONS Somatostatin receptor scintigraphy might be useful in the visualisation of non-iodine avid PTC metastases and demonstrat-ing the expression of somatostatin receptors that are potential therapeutic targets.