Serum Visfatin does not seem to be a Useful Marker to Guide Glucocorticoid Substitution in Adrenal Insufficiency.

Primary adrenal insufficiency (Addison's disease, AD) requires lifelong steroid substitution. Excess exogenous glucocorticoids promote abdominal obesity, insulin-glucose imbalance, and hypertension. Reliable markers of the adequate glucocorticoid replacement are lacking. Visfatin is a pro-inflammatory adipokine, with enzymatic activity of nicotinamide phosphoribosyltransferase. It enhances leukocyte function and synthesis of tumour necrosis factor α (TNFα) and interleukin-6 (IL-6). Serum visfatin is elevated in autoimmunity, but also in obesity, insulin resistance, and metabolic syndrome. This study was aimed to investigate whether serum visfatin could guide the glucocorticoid substitution in AD. Biochemical analyses were performed in 96 patients with AD (mean age 43.3±14.9 years) and 91 controls (43.5±12.5 years). Visfatin level was significantly elevated in patients with AD compared to controls (p<0.0001). Higher circulating IL-6 was also detected among subjects with AD (p=0.006). In AD, visfatin level was positively correlated with IL-6 (p=0.014), TNFα (p=0.001), body mass (p=0.015), fasting insulin (p=0.001) and HOMA-IR (p=0.001). No relationship was noticed with daily hydrocortisone (p=0.096) and urinary free cortisol excretion (p=0.499). Only the correlations with IL-6 and fasting insulin survived multiple regression analysis (p=0.049 and p=0.005, respectively). Additionally, positive correlation between visfatin and autoantibodies to 21-hydroxylase was noted (p=0.005). In the control group serum visfatin was correlated with IL-6 (p=0.009) and TNFα (p=0.0002). The current study reveals elevated serum visfatin in autoimmune AD. Visfatin does not seem a useful marker of the glucocorticoid replacement, although it correlates with fasting insulin and pro-inflammatory molecules. Further functional analyses are warranted to elucidate the role of visfatin in autoimmunity.

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.

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.

99mTc-EDDA/HYNIC-TOC in the diagnosis of differentiated thyroid carcinoma refractory to radioiodine treatment.

BACKGROUND: In majority of cases of differentiated thyroid carcinoma (DTC), the ablative radioiodine treatment shows high efficacy. In a small number of patients, mechanism of selective iodine uptake by the DTC cells is insufficient and alternative methods of diagnosis and treatment are needed. As demonstrated in vitro, DTC cells show expression of somatostatin recep-tors. Radiolabeled somatostatin analogs are widely used in the diagnosis of neuroendocrine tumors. The aim of the study was to evaluate the utility of peptide receptor scintigraphy with the use of 99mTc-EDDA/HYNIC-TOC in the diagnosis of DTC in patients with elevated thyroglobulin concentrations (Tg), negative WBS and no effect of the consecutive radioiodine therapies. MATERIAL AND METHODS: Whole body scintigraphy as well as SPECT of neck and chest were performed 3 and 24 h after i.v. administration of 740 MBq 99mTc-EDDA/HYNIC-TOC. The obtained images were compared with other radionuclide and ra-diological imaging methods. Forty-three patients with DTC after surgery and ablative radioiodine treatment with negative WBS and elevated Tg were qualified. Patients' age: 18-83 years (mean 58.0). RESULTS: SRS showed foci of tracer accumulation in 29 cases (67.4%). Sensitivity was 69.0% specificity 78.6%. SRS correctly identified local recurrence in 8 pts., metastatic lymph nodes in 19 pts., lung metastases in 12 pts. and bone metastases in 5 pts. SRS showed high sensitivity in the detection of metastatic lymph nodes (100%) and bone metastases (83.3%) and lung metastases (63.2%). Positive SRS was found in pts. with higher Tg concentrations (130 ± 144 vs. 30 ± 54 ng/ml). CONCLUSION: Scintigraphy with the use of the studied technetium-99m-labeled somatostatin analog is useful in the evaluation of patients with advanced DTC. It shows relatively good sensitivity and specificity but not high enough to be recommended as a routine imaging method. The role of somatostatin receptor scintigraphy in DTC is complementary to other imaging modalities.

Positive autoantibodies to ZnT8 indicate elevated risk for additional autoimmune conditions in patients with Addison's disease.

Autoimmune Addison's disease (AAD) associates with exceptional susceptibility to develop other autoimmune conditions, including type 1 diabetes (T1D), marked by positive serum autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and insulinoma-associated protein 2 (IA-2A). Zinc transporter 8 (ZnT8) is a new T1D autoantigen, encoded by the SLC30A8 gene. Its polymorphic variant rs13266634C/T seems associated with the occurrence of serum ZnT8 antibodies (ZnT8A). This study was designed to determine the prevalence of serum ZnT8A and their clinical implication in 140 AAD patients. Other beta cell and thyroid-specific autoantibodies were also investigated, and ZnT8A results were confronted with the rs13266634 genotype. ZnT8A were detectable in 8.5 %, GADA in 20.7 %, IA-2A in 5.7 %, IAA in 1.6 % and various anti-thyroid antibodies in 7.1-67.8 % individuals. Type 1 diabetes was found in 10 % AAD patients. ZnT8A were positive in 57.1 % of T1D patients and 3.4 % non-diabetic AAD. Analysis of ZnT8A enabled to identify autoimmunity in two (14.3 %) T1D individuals previously classified as autoantibody-negative. ZnT8A-positive patients revealed significantly higher number of autoimmune conditions (p < 0.001), increased prevalence of T1D (p < 0.001) and other beta cell-specific autoantibodies. Carriers of the rs13266634 T-allele displayed increased frequency (p = 0.006) and higher titres of ZnT8A (p = 0.002). Our study demonstrates high incidence of ZnT8A in AAD patients. ZnT8A are associated with coexisting T1D and predictive of T1D in non-diabetic subjects. Moreover, positive ZnT8A in AAD indicate elevated risk for additional autoimmune conditions. Autoantibodies to beta cell antigens, comprising ZnT8, could be included in routine screening panels in AAD.

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.

Diagnosis, treatment, and prognosis in patients with liver metastases from follicular thyroid carcinoma (FTC).

Follicular thyroid carcinoma (FTC) is the second most common type of thyroid cancer (TC) and accounts for approximately 10% of all TC cases. Liver metastases are a rare presentation in 0.5-1% of follicular thyroid cancers, usually occurring in the setting of widely disseminated FTC disease, and their presence is associated with poor prognosis. Until now, there have been only 30 cases of FTC liver metastases described in the literature. Herein, we review publications and describe diagnostic tools that may be used in the diagnosis and follow-up of FTC metastases to the liver, including biopsy and imaging techniques like US, CT, MRI, SPECT, PET, and radioiodine scintigraphy. We also present and discuss current methods of treatment, e.g. TSH suppressive therapy with levothyroxine, surgery, radiofrequency ablation (RFA), transarterial embolisation (TAE), liver transarterial chemoembolisation (TACE), chemotherapy with cisplatin and doxorubicin, treatment with Indium- 111-octreotide (or its analogues), and tyrosine kinase inhibitors (sorafenib, sunitinib). At the end we describe the course, results of diagnostics, and treatment in a patient with large multiple FTC metastases to the liver. (Endokrynol Pol 2016; 67 (3): 332-347).

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.

Steroid replacement in primary adrenal failure does not appear to affect circulating adipokines.

Despite continuous efforts for an optimal steroid replacement, recent observations suggest increased cardiometabolic risk and related mortality in primary adrenal insufficiency (PAI). Adipokines are peptides from the adipose tissue, markers of cardiometabolic dysfunction. This study was aimed to evaluate serum levels of adipokines: leptin, adiponectin, and resistin in PAI during conventional steroid substitution. The analysis comprised 63 patients (mean age 42.7 ± 14.1 years) and 63 healthy controls. Serum adipokines, lipid profile, and plasma glucose were assessed in both cohorts. ACTH, serum insulin, HOMA-IR, DHEA-S, cortisol and 24 h urinary free cortisol were determined in PAI. Body mass composition was analyzed by Dual-Energy X-ray Absorptiometry. Mean BMI in the control group was 24.1 ± 3.9 kg/m(2) and 23.7 ± 3.9 kg/m(2) in the PAI cohort. Serum leptin and adiponectin levels were similar in both groups, whereas resistin appeared significantly lower among affected subjects (p = 0.0002). Its levels were weakly correlated with HOMA-IR (p = 0.048). Leptin was independently correlated with fasting insulin, HOMA-IR, BMI, and body fat (p < 0.001). At the multiple regression analysis only weight (p = 0.017), total and HDL cholesterol (p < 0.001) appeared significant predictors of adiponectin level. No adipokine correlations with serum cortisol or daily hydrocortisone dose were found. Patients receiving DHEA substitution displayed lower leptin and adiponectin levels (p < 0.05). In conclusion, our study did not provide evidence of an adverse adipokine profile in patients with PAI under conventional glucocorticoid replacement. Serum adipokines in treated PAI follow similar correlations to those reported in healthy subjects. Further prospective studies are warranted to verify and explain plausible excess of cardiovascular mortality in PAI.

Peptide receptor radionuclide therapy of differentiated thyroid cancer: efficacy and toxicity.

In rare cases of differentiated thyroid carcinoma (DTC), radioiodine treatment is no longer effective due to cell dedifferentiation. Targeting somatostatin receptors in DTC cells by radiolabelled somatostatin analogues could provide an alternative therapy option. The aim of this study was to evaluate safety and efficacy of peptide receptor radionuclide therapy (PRRT) in patients with advanced, non-iodine avid DTC. Eleven patients aged 47-81 years (median: 65 years) with a history of several courses of radioiodine therapy, increasing thyroglobulin (Tg) and negative whole body scan, were qualified to the study. After confirming receptor expression by somatostatin receptor scintigraphy, PRRT with yttrium-90 labelled analogue was initiated. Fractionated treatment protocol was used with four doses of (90)Y-DOTA-TOC in 12-week intervals. Activity of each dose was 3.7 GBq (100 mCi). Of 11 patients, 5 died before receiving the fourth course of PRRT. In the remaining six patients, morphological response, evaluated 3 months after the last course using RECIST criteria showed partial remission (PR) in one patient, stable disease (SD) in two patients and progressive disease (PD) in three patients. Biochemical response based on Tg measurements before and after PRRT showed PR in one patient, SD in four patients and PD in one patient. Median survival was 21 months from the first course of PRRT. Only minor and transient hematological toxicity was observed in some patients. We conclude that PRRT is generally well-tolerated and may be a valuable option for some patients with radioiodine-refractory DTC.

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.

The feasibility and efficacy of secondary neck dissections in thyroid cancer metastases.

The purpose of the study was to assess the feasibility of secondary neck dissections (ND) in different types of thyroid cancer (TC), to evaluate the influence of ND extent on morbidity and to describe biochemical and clinical outcomes. 51 patients previously operated for TC (33-well differentiated TC-WDTC, 15 medullary TC-MTC, 3 poorly differentiated TC-PDTC) presenting detectable nodal disease. Reoperations covered I-VII neck levels. Radical neck dissection was performed in 22 patients, selective neck dissection in 29 patients. 14 central compartment (CC), 10 mediastinal and 41 level IV excisions were performed. Postoperative complications occurred in 13 patients: 4 chyle leaks, 3 massive bleedings, 8 permanent vocal cord pareses, hypoparathyroidism in 22 patients (43.1%), 2 patients expired in perioperative period. In WDTC: in seven patients thyroglobulin level normalized directly after ND, in ten patients in the follow-up; six patients developed distant metastases. None of the patients with MTC achieved calcitonin level <10 pg/ml; nine patients developed distant metastases. None of the patients with PDTC achieved Tg <2 mg/ml; two patients died, the third developed distant metastases. Secondary ND in TC present a challenge by means of surgical approach and possibility of complications. In MTC and PDTC the long-term results were unsatisfactory. In WDTC, the secondary ND should be performed due to strong indications. Metastases localization in levels IV, VI, VII were connected with high complication rate, but these surgeries were crucial for satisfactory oncological outcomes.

Struma ovarii maligna.

INTRODUCTION: Malignant struma ovarii is a rare ovarian neoplasm composed predominantly of mature thyroid tissue. CASE REPORT: A right ovarian tumor was discovered at ultrasound examination in a 20-year-old woman. Complete right ovariectomy was done - histopathological examination revealed papillary thyroid carcinoma arising in struma ovarii (malignant struma ovarii). Patient underwent subsequent total thyroidectomy - the thyroid was found to be without any pathological lesions. After operations the patient received ablative radioiodine treatment (200 mCi 131I). An 131I posttherapeutic whole-body radioiodine scintigraphy was performed and showed uptake in bone metastases. L-thyroxine TSH suppresive doses followed radioiodine ablation and thyroglobulin level is monitored. Next doses of radioiodine has been scheduled. DISCUSSION: Authors suggest that the management of malignant struma ovarii should be the same as differentiated thyroid cancer, so after surgical excision of ovarian neoplasm, we recommend thyroidectomy, radiotherapy with 131I and levothyroxine suppressive therapy. Long-term follow-up for the detection of metastases or tumor recurrence by serial serum thyroglobulin measurements and 131I scan may be required in patients with this rare tumor.

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.

Combined octreotide and peptide receptor radionuclide therapy ((90)Y-DOTA-TATE) in case of malignant insulinoma.

BACKGROUND: Insulinomas are the most common functioning neuroendocrine tumours of the pancreas. Hypoglycemia due to excessive production of insulin is a main feature of this disease. Usually these neoplasms are benign and single with surgical excision as a treatment of choice. About 10% are malignant with tendency to form metastases especially to the liver then therapy requires various medical technics. CASE REPORT: 43 years old female with reccurent syncopies in course of hypoglycemia was admitted to the hospital to be diagnosed. Having suspected pathology within the pancreas the abdominal MRI was performed. It showed presence of numerous metastatic changes in the liver with no any other deviations in the abdomen including pancreas. Subsequent 18FDG PET-CT revealed metastases to the regional lymph nodes and the liver and suggested the presence of a primary lesion in the tail of the pancreas which was confirmed in EUS. Surgical excision of the tail of the pancreas was done. Pathological result: pancreatic neuroendocrine well differetiated cancer. Due to the recurrence of hypoglycemia patient was admitted to Department of Endocrinology where somatostatin analogue scintigraphy showed the presence of tracer accumulation foci in the liver. Combined long-acting somatostatin analogue (octreotide) and peptide radionuclide receptor ((90)Y-DOTA-TATE) therapy were introduced. Stable blood glucose levels with no tendency to hypoglycemia and partial regression (PR) of liver lesions according to RECIST citeria were observed in course of the treatment.

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).

[Metabolic assessment of hydrocortisone replacement therapy in patients with primary adrenocortical insufficiency]. / Ocena metaboliczna terapii substytucyjnej hydrokortyzonem u pacjentów z pierwotna niedoczynnoscia kory nadnerczy.

Primary adrenocortical insufficiency (Addison's disease) requires lifelong steroid substitution. Although the patients are both at risk of under-replacement and excessive glucocorticoid exposure, there is no consensus on monitoring this therapy. The aim of the study was to assess the substitution therapy in Addison's disease in regard to metabolic balance, glycaemic effects and bone mineral density. Seventy two subjects with primary adrenal insufficiency (52 women, 20 men) were evaluated. Mean disease duration was 15.6 years. All patients were supplemented with hydrocortisone (10-60 mg/day), 45 also used fludrocortisone, and 8 - dehydroepiandrosterone. The patients underwent medical examination, assessment of glycaemia and electrolyte parameters, and hormonal analyses. Bone mineral density was evaluated in 65 individuals. Mean blood pressure in patients was 117/74 mmHg and positively correlated with age (p < 0.001). No correlation was found between the daily hydrocortisone dose and blood pressure nor electrolyte parameters. Mean morning serum cortisol before hydrocortisone administration was 27 +/- 42 nmol/l, 2 hours later 904 +/- 263 nmol/l, 222 +/- 226 nmol/l before the afternoon dose, and 219 +/- 192 nmol/l around 22.00. Mean 24h urinary cortisol excretion was 521.5 +/- 387 nmol, and morning plasma ACTH was 398.9 +/- 423 pg/ml. Fasting serum glucose was 83.6 +/- 12.6 mg/dl. Fasting glycaemia and insulinaemia did not correlate with hydrocortisone dose but did present a positive correlation with body mass and age. Sixteen patients were diagnosed with osteoporosis in the lumbar spine, and 6 women--in femoral neck. Bone mineral density correlated positively with serum DHEA-S, and negatively with the patient's age, duration of the Addison's disease and total steroid dose administered during the therapy. In conclusion, the steroid substitution in Addison's disease requires individually tailored dosage and adequate monitoring. The factors which may potentially contribute to the development of adverse effects of the glucocorticoid over-supplementation are age, duration of the Addison's disease and total administered steroid dose.

Screening for associated autoimmune disorders in Polish patients with Addison's disease.

Autoimmune Addison's disease (AAD) is the main reason of primary adrenal failure. More than a half of patients display additional autoimmune conditions, which represent a considerable clinical concern. This study aimed to investigate the prevalence of concomitant autoimmune disorders in 85 Polish AAD patients (61 females, 24 males). Mean age at AAD onset was 34.6 ± 12.6 years, significantly earlier in males (P < 0.001). Sixty-nine patients presented positive serum antibodies to 21-hydroxylase and shorter AAD duration than those with negative results (P = 0.027). Seventy-three subjects suffered from coexisting autoimmune disorders. Serum autoantibodies against thyreoperoxidase, thyroglobulin, TSH receptor, glutamic acid decarboxylase, insulin, tyrosine phosphatase-like protein IA2, parietal cell H(+)/K(+)-ATPase, intrinsic factor and tissue transglutaminase were detectable in 71.8, 41.2, 4.7, 21.0, 4.9, 2.5, 49.4, 12.0 and 3.5% of patients, respectively. Antinuclear antibodies were found in 12.5%. Thyroid autoimmunity was most common (46 subjects with lymphocytic thyroiditis, 19 with Graves' disease), followed by atrophic gastritis (29.4%), pernicious anaemia (11.8%), hypergonadotropic hypogonadism (8.2%), vitiligo (8.2%), type 1 diabetes (7.1%), celiac disease (3.5%) and alopecia (2.4%). Gender differences were observed only for thyroid autoimmunity. Current study confirms particular tendency of AAD patients to develop other autoimmune disorders. Active search for concomitant conditions is warranted to prevent serious complications.

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

Autoimmune Addison's 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.