The Current Role of Parathyroid Fine-Needle Biopsy (P-FNAB) with iPTH-Washout Concentration (iPTH-WC) in Primary Hyperparathyroidism: A Single Center Experience and Literature Review.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is a condition characterized by disorders of calcium-phosphate metabolism and bone metabolism caused by pathological overproduction of parathyroid hormone (PTH). The diagnosis of overt PHPT is based on the presence of clinical symptoms and laboratory abnormalities typical of this condition: hypercalcemia, hypercalciuria and elevated iPTH levels. Imaging studies are not used for diagnostic purposes; they are performed to localize the parathyroid glands prior to potential surgical treatment. Technetium 99 m sestamibi scintigraphy (Tc99 m-MIBI) is the gold standard in the assessment of pathologically altered parathyroid glands. Other diagnostic options include cervical ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). Parathyroid biopsy (P-FNAB) with iPTH washout concentration (iPTH-WC) assessment is still an underestimated method of preoperative parathyroid gland localization. Few studies have reported the utility of US-guided P-FNAB in preoperative assessment of parathyroid lesions. The aim of the study was to present our experience with 143 P-FNAB with iPTH-WC assessment. MATERIAL AND METHODS: Laboratory results, US findings, P-FNAB complications and comparison with other imaging techniques were described and analyzed. RESULTS: In 133 (93.0) patients, iPTH washout-to-serum ratio exceeded threshold level 0.5 and were classified as positive results. Median iPTH-WC in this group was 16,856 pg/mL, and the iPTH-WC to serum iPTH ratio was 158. There was no correlation between iPTH-WC and serum PTH, serum calcium, parathyroid gland volume and shape index. In the group of 46 operated patients, 44 demonstrated positive iPTH-WC results, which corresponds to a sensitivity of 95.6%. In Tc99-MIBI, radiotracer retention was found in 17 cases (in 24 MIBI performed), which corresponds to a sensitivity of 52.2%. P-FNAB did not cause any major side effects -92.5% of all patients had no or mild adverse events after this procedure. CONCLUSIONS: P-FNAB with iPTH-WC is a reliable method in parathyroid adenoma localization during PHPT. Its sensitivity for diagnosis of PHPT is much higher than that of Tc99-MIBI, and in some situations, P-FNAB with iPTH-WC may even replace that method. Furthermore, cost-effectiveness of iPTH-WC is at least similar to that of Tc99-MIBI. Complications of P-FNAB are mild and we can describe this method as a safe procedure.

Progress on Genetic Basis of Primary Aldosteronism.

Primary aldosteronism (PA) is a heterogeneous group of disorders caused by the autonomous overproduction of aldosterone with simultaneous suppression of plasma renin activity (PRA). It is considered to be the most common endocrine cause of secondary arterial hypertension (HT) and is associated with a high rate of cardiovascular complications. PA is most often caused by a bilateral adrenal hyperplasia (BAH) or aldosterone-producing adenoma (APA); rarer causes of PA include genetic disorders of steroidogenesis (familial hyperaldosteronism (FA) type I, II, III and IV), aldosterone-producing adrenocortical carcinoma, and ectopic aldosterone-producing tumors. Over the last few years, significant progress has been made towards understanding the genetic basis of PA, classifying it as a channelopathy. Recently, a growing body of clinical evidence suggests that mutations in ion channels appear to be the major cause of aldosterone-producing adenomas, and several mutations within the ion channel encoding genes have been identified. Somatic mutations in four genes (KCNJ5, ATP1A1, ATP2B3 and CACNA1D) have been identified in nearly 60% of the sporadic APAs, while germline mutations in KCNJ5 and CACNA1H have been reported in different subtypes of familial hyperaldosteronism. These new insights into the molecular mechanisms underlying PA may be associated with potential implications for diagnosis and therapy.

Coexistence of DiGeorge syndrome with Fahr syndrome, mosaic Turner syndrome and psychiatric symptoms - a case report. / Zaburzenia psychiatryczne u pacjentki z zespolem DiGeorge'a, zespolem Fahra i zespolem Turnera ­ opis przypadku.

We report a case of a 63-year-old patient with psychiatric symptoms diagnosed with coexisting DiGeorge syndrome, Fahr syndrome and Turner syndrome. To our knowledge, this is the first reported case of coexistence of DiGeorge syndrome and mosaic Turner syndrome. Basal ganglia calcification, known as Fahr syndrome, may develop in patients with DiGeorge syndrome as a consequence of calcium-phosphate balance disturbances resulting from primary hypoparathyroidism. A deletion of chromosome 22q11.2 in DiGeorge syndrome, basal ganglia calcification and, according to some research, mosaic Turner syndrome independently can lead to psychiatric disorders. A leading clinical manifestation of the genetic diseases in our patient was long-term, drug-resistant depression with sleeping disorders and organic hallucinosis. Affective disorders led the patient to attempt suicide. The aim of the study was to highlight the importance of perceiving subtle findings which can lead to a diagnose of a genetic disease in a patient with mental health issues. We also discuss the predisposition to psychiatric disorders in DiGeorge syndrome, Turner syndrome and Fahr syndrome.

Hypereosinophilia in Solid Tumors-Case Report and Clinical Review.

BACKGROUND: Renal cell cancer may cause various paraneoplastic syndromes; however, paraneoplastic hypereosinophilia occurs exceedingly rare. Thus far, only two cases of clear cell renal cell carcinoma (CCRCC) associated with hypereosinophilia have been reported. In this paper, we present a case of paraneoplastic hypereosinophilia associated with renal cell carcinoma and a review of the reported cases of hypereosinophilia in solid tumors. METHODS: The review is based on an electronic literature search performed in the PubMed database in September 2020 with the following key terms: eosinophilia & neoplasm; eosinophilia & cancer; eosinophilia & paraneoplastic syndrome. Papers were included based on screening the titles and/or abstracts. We also included the case of our patient in the analysis. CASE PRESENTATION: A 68-year-old Caucasian female patient with recurrent CCRCC was admitted to our Clinic for exacerbating dyspnea and chest and right upper abdominal pain, accompanied by confusion. Preliminary blood tests showed an increased white blood cell count of 40,770/µl, and an increased eosinophil count of 6,530/µl indicating eosinophilia. Several tests were carried out to rule out the noncancer causes of hypereosinophilia. The temporal appearance of eosinophilia and the recurrence of CCRCC without any other apparent potential causes led to the diagnosis of paraneoplastic hypereosinophilia. Despite treating with high doses of corticosteroids, only a transient decrement in eosinophil count was observed along with further deterioration of the patient's condition. The patient succumbed to the disease 6 months following the tumor surgery and 2 months after the diagnosis of hypereosinophilia and tumor recurrence. CONCLUSION: Our observations are in agreement with the majority of reports showing that the occurrence of eosinophilia following tumor resection may indicate a poor prognosis, tumor recurrence, and rapid disease progression.

Low incidence of focal lesions in the thyroid glands of patients with hereditary haemochromatosis - a single-centre study from Poland.

INTRODUCTION: Hereditary haemochromatosis (HH) is a disease characterised by the excessive absorption of iron and its deposition in various organs. Late complications of this disease include cirrhosis, hepatocellular carcinoma, and endocrine disorders. Data from the literature on thyroid disorders in patients with HH are inconsistent and ambiguous, and no research has been done to determine the relationship between excessive accumulation of iron and the thyroid morphology. Therefore, the aim of this study was to characterise thyroid function and ultrasound images in patients with clinically overt hereditary haemochromatosis. MATERIAL AND METHODS: We studied 40 patients who were diagnosed with hereditary haemochromatosis with one of the mutations of the HFE gene and iron deposits in liver in specimen from liver biopsies (graded G2 to G4) or in MRI. To assess thyroid function, ultrasound examinations of the thyroid gland were performed and serum TSH concentrations were measured. RESULTS: We showed in our study that patients with HH have been diagnosed with thyroid focal lesions statistically less frequent than in the control group. We did not reveal any statistically significant difference in TSH concentration between patients with HH and the general population. However, patients with more severe iron deposits in liver showed lower TSH concentration. CONCLUSIONS: Our results indicate lower incidence of focal lesions in thyroid gland in a group of patients with clinically overt hereditary haemochromatosis.

The Role of Immunotherapy in the Treatment of Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is a rare epithelial neoplasm, with a high tendency for local invasion and distant metastases, with limited treatment options. Surgical treatment is the method of choice. For decades, the mainstay of pharmacological treatment has been the adrenolytic drug mitotane, in combination with chemotherapy. Immunotherapy is the latest revolution in cancer therapy, however preliminary data with single immune checkpoint inhibitors showed a modest activity in ACC patients. The anti-neoplastic activity of immune checkpoint inhibitors such as anti-cytotoxic-T-lymphocyte-associated-antigen 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), and anti-PD-ligand-1 (PD-L1) antibodies in different solid tumors has aroused interest to explore the potential therapeutic effect in ACC as well. Multiple ongoing clinical trials are currently evaluating the role of immune checkpoint inhibitors in ACC (pembrolizumab, combination pembrolizumab and relacorilant, nivolumab, combination nivolumab and ipilimumab). The primary and acquired resistance to immunotherapy continue to counter treatment efficacy. Therefore, attempts are made to combine therapy: anti-PD-1 antibody and anti-CTLA-4 antibody, anti-PD-1 antibody and antagonist of the glucocorticoid receptor. The inhibitors of immune checkpoints would benefit patients with antitumor immunity activated by radiotherapy. Immunotherapy is well tolerated by patients; the most frequently observed side effects are mild. The most common adverse effects of immunotherapy are skin and gastrointestinal disorders. The most common endocrinopathy during anti-CTLA treatment is pituitary inflammation and thyroid disorders.

When you hear hooves, you should look for... zebras.

Not required for Clinical Vignette.

Medullary thyroid carcinoma of unknown primary origin with synchronous finding of papillary thyroid carcinoma.

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Effects of thyroid hormone imbalance on colorectal cancer carcinogenesis and risk - a systematic review.

Colorectal cancer (CRC) is the second leading cause of cancer-related death. The prevalence of colorectal neoplasm is increasing. Many studies have shown that thyroid dysfunction may be connected with the higher risk of pancreatic and breast cancer, but only a few described the role of thyroid dysfunction and thyroid hormone (TH) replacement in the development and risk of CRC. The aim of this study is to summarise all findings and potentially elucidate the connection between TH imbalance and colorectal cancer. The systematic review was conducted according to PICO and PRISMA guidelines. We searched MEDLINE, ClinicalTrials.gov, www.clinicaltrialsregister.eu, and Cochrane Library databases using the following keywords: "((((thyroid OR hypothyroidism OR hyperthyroidism OR levothyroxine OR hashimoto OR graves OR thyroidectomy)) AND (colon OR colorectal OR CRC)) NOT hashimoto[Author]) NOT graves[Author])". No filters were used. Of total of 3054 articles identified by the search strategy, 11 met PICO criteria and were included into the review. Four of those were on cell lines and seven were human studies. Analysis of the included studies revealed an elevated risk of CRC in patients with hypothyroidism with aORs ranging from 1.16 (95% CI: 1.08-1.24, p < 0.001) to 1.69 (95% CI: 1.21-2.36, p = 0.002). Moreover, TH replacement therapy has a protective effect for CRC risk with aOR ranging from 0.60 (95% CI: 0.44-0.81, p = 0.001) to 0.92 (95% CI: 0.86-0.98, p = 0.009). THs seem to play a role in colorectal carcinogenesis. Further studies are warranted to define the exact role of thyroid hormone imbalance in prevention and treatment of CRC.

Adrenal hemorrhage: A single center experience and literature review.

BACKGROUND: Adrenal hemorrhage (AH) is a rare condition that can lead to acute adrenal insufficiency and may be fatal. The risk factors of AH include focal adrenal lesion, abdominal trauma and anticoagulation therapy. The clinical manifestation of AH varies widely; the symptoms may be related to adrenal insufficiency or may reflect multiple organ failure. However, in many cases, the course of AH is asymptomatic. OBJECTIVES: The study is a retrospective analysis of 23 cases of AH, whose aim is to discuss the etiology and the management of selected patients, as well as a literature review. MATERIAL AND METHODS: The paper presents a retrospective analysis of 23 patients with AH confirmed by radiological and/or pathological examination. Epidemiological data, the results of laboratory tests, and radiological and pathological examinations were included in the analysis. RESULTS: The risk factors of AH were not established in 13 patients, 5 patients had experienced a trauma prior to AH diagnosis, 1 patient was diagnosed with sepsis, 2 patients had concomitant neoplastic disease, and in 2 patients, 2 risk factors were present. Among patients who required emergency admission, 5 patients were hospitalized due to acute abdominal pain, 1 patient due to sepsis and 1 patient due to symptoms of active endocrinopathy. In the remaining patients, diagnostic procedures were prompted by the detection of adrenal incidentaloma (AI). A total of 40% of patients underwent surgical treatment due to the magnitude of AH or clinical and laboratory evidence of overt endocrinopathy. In the remaining patients, conservative treatment and further observation was recommended. In 34.8% of these patients, follow-up examinations revealed a gradual regression. CONCLUSIONS: It seems that there is a need to distinguish patients with AH who do not require surgical intervention. Follow-up radiological examination is necessary to reassess the lesion. The patients in whom shrinkage of the tumor can be observed are likely not to require surgical treatment.

Epidemiology, risk factors and prognosis of Interferon alpha induced thyroid disorders. A Prospective Clinical Study.

INTRODUCTION: Hepatitis C virus (HCV) infection is a worldwide problem and hepatitis, which is its natural unfavourable course, is still a challenge for hepatologist. At present, standards of treatment are changing from combined therapy with interferon alpha (IFN-α) and ribavirin to new antiviral drugs. The current classification divides interferon induced thyroid diseases (IITD) into two groups: autoimmune (Hashimoto disease, Graves disease, positive antithyroid autoantibodies in euthyroid patients) and non-autoimmune (destructive thyroiditis, non-autoimmune hypothyroidism). A common complication of cytokine therapy is the induction of antithyroid autoantibodies de novo without thyroid dysfunction. During therapeutic regimens combined with ribavirin, destructive thyroiditis with typical biphasic course is more common than in IFN-α monotherapy. Clinically, overt pathologies often have discrete symptoms, which cause diagnostic and therapeutic dilemmas. AIMS: The aim of this study was to estimate IITD occurrence, to find risk factors for IITD development. MATERIAL AND METHODS: The study group consisted of 66 patients treated for HCV infection. Before and during antiviral therapy, hormonal (TSH, fT4, fT3), immunological (thyroid autoantibodies), ultrasonographic and genetic (HLA-A2) parameters were evaluated. RESULTS: Hormonal disturbances were detected in 24.2% of patients; however, 43.9% of patients had positive thyroid autoantibodies (de novo) without hormonal imbalance. Multivariate analysis revealed the following: female sex, elevated TSH level, occurrence of anti-TPO autoantibodies (TPO-Ab), and increased blood velocity in thyroid arteries are risk factors for IITD development. IN CONCLUSION: Thyroid disorders are common during IFN-α therapy. Previous epidemiological data seem to be underestimated. Important risk factors for IITD development are: female sex, elevated serum TSH concentration (≥2.5 µU/mL), positive TPO-Ab and increased blood velocity in thyroid arteries.

Self-diagnosis of hyperparathyroidism during pregnancy resulting in parathyroidectomy and uncomplicated delivery.

Primary hyperparathyroidism is a condition with hypercalcemia and elevated parathyroid hormone (PTH). Typically, treating patients with such disease does not pose a problem for doctors, unless the patient is pregnant. Firstly, pregnancy may mask signs of hypercalcemia. Secondly, treatment should be applied with special care for immature fetus. If undiagnosed and untreated, it is life-threatening for the mother and the baby. The main cause of primary hyperparathyroidism is parathyroid adenoma, which should be removed surgically in second trimester. If the patient is monitored by a multidisciplinary team, the risk of mortality and pregnancy loss is reduced.

A case report of Gitelman syndrome resulting from two novel mutations in SLC12A3 gene / El caso del síndrome de Gitelman causado por dos nuevas mutaciones en el gen SLC12A3

Introduction: Hypokalaemia is a common clinical problem. A potential but commonly overlooked cause of hypokalaemia is Gitelman syndrome. Material and methods: A 26-year-old man was admitted to the hospital due to syncope with general and muscular weakness and muscle cramps. The patient's history revealed previous recurrent syncope events associated to hypokalaemia with the lowest serum potassium value being 2.6mmol/l. At admission, blood pressure was normal and no changes were found at physical examination. Laboratory tests showed mild hypokalaemia (3.0mmol/l), hypomagnesaemia (1.36mg/dl), hypocalciuria (< 40mg/24h), and metabolic alkalosis (HCO3− 29.7mmol/l, BE 5.3mmol/l). Results: Further laboratory tests (FeK, TTKG) confirmed inappropriate kaliuresis. Conn's disease was excluded by hormonal and imaging assessments. Genetic testing was performed and two novel heterozygous mutations: c.35_36insA and c.1095+5G>A were found in transcriptNM_000339.2 in SLC12A3 gene. Conclusion: The patient was diagnosed with Gitelman syndrome and was treated with supplements of potassium and magnesium (AU)

Introducción: La hipopotasemia es un problema clínico común. El síndrome de Gitelman es una posible causa de hipopotasemia a veces no reconocida. Material y métodos: Un hombre de 26 años de edad ingresa en un hospital por causa de un síncope, debilidad generalizada y calambres musculares. La historia clínica del paciente reveló la incidencia del síncope con hipopotasemia recurrente con el valor más bajo de potasio en 2,6mmol/l. En el ingreso, el paciente presentaba una presión arterial normal y la exploración física no reveló ninguna enfermedad. La evaluación del laboratorio demostró una hipopotasemia leve (K+ 3,0mmol/l), hipomagnesemia (Mg 1,36mg/dl), hipocalciuria (<40mg/24h) y alcalosis metabólica (HCO3- 29,7mmol/l, exceso de base 5,3mmol/l). Resultados: Otras pruebas de laboratorio (FeK, TTKG) confirman una caliuresis inadecuada. La enfermedad de Conn fue excluida tras la evaluación hormonal y radiológica. Se realizaron las pruebas genéticas y 2 mutaciones heterocigóticas: c.35_36insA y c.1095+5G>A fueron encontradas en la transcripción NM_000339.2 del gen SLC12A3. Conclusión: El paciente fue diagnosticado con el síndrome de Gitelman y fue tratado con suplementos de potasio y magnesio (AU)

A case report of Gitelman syndrome resulting from two novel mutations in SLC12A3 gene.

INTRODUCTION: Hypokalaemia is a common clinical problem. A potential but commonly overlooked cause of hypokalaemia is Gitelman syndrome. MATERIAL AND METHODS: A 26-year-old man was admitted to the hospital due to syncope with general and muscular weakness and muscle cramps. The patient's history revealed previous recurrent syncope events associated to hypokalaemia with the lowest serum potassium value being 2.6mmol/l. At admission, blood pressure was normal and no changes were found at physical examination. Laboratory tests showed mild hypokalaemia (3.0mmol/l), hypomagnesaemia (1.36mg/dl), hypocalciuria (< 40mg/24h), and metabolic alkalosis (HCO3(-) 29.7mmol/l, BE 5.3mmol/l). RESULTS: Further laboratory tests (FeK, TTKG) confirmed inappropriate kaliuresis. Conn's disease was excluded by hormonal and imaging assessments. Genetic testing was performed and two novel heterozygous mutations: c.35_36insA and c.1095+5G>A were found in transcript NM_000339.2 in SLC12A3 gene. CONCLUSION: The patient was diagnosed with Gitelman syndrome and was treated with supplements of potassium and magnesium.

Hormonal activity in clinically silent adrenal incidentalomas.

INTRODUCTION: The rapid development of modern imaging techniques, has led to an increase in accidentally discovered adrenal masses without clinically apparent hormonal abnormalities. Such tumours have been termed "incidentalomas". The diagnostic work-up in patients with adrenal incidentalomas is aimed at the determination of hormonal activity of the tumour and identification of patients with potentially malignant tumours. The aim of our study was a retrospective analysis of selected clinical characteristics and hormonal studies in accidentally discovered adrenal tumours. MATERIAL AND METHODS: Fourty hundred sixty-three patients with serendipitously discovered adrenal masses, diagnosed and treated in the Department of Endocrinology and Internal Diseases, Medical University of Gdansk as well as in the affiliated Endocrinology Clinic between 1993 and October of 2009 were included in the analysis. Out of all patients, 245 were referred for adrenalectomy. RESULTS: We found that clinically "silent" tumours often demonstrate subclinical hormonal activity. In our report, increased 24-h urinary excretion of cortisol correlated positively with tumour size (p < 0.001). Moreover, a statistical relationship was demonstrated between tumour size and serum cortisol concentration assessed in the 1 mg dexamethasone suppression test (p < 0.001). Increased values of dehydroepiandrosterone/dehydroepiandrosterone sulphate were more often found in malignant than in benign tumours (p < 0.01). Urinary concentrations of 17-ketosteroids correlate positively with diagnosis of adrenocortical cancer (p = 0.02). CONCLUSIONS: We found that clinically "silent" tumours often demonstrate subclinical hormonal activity (subclinical Cushing syndrome, subclinical pheochromocytoma, low-symptomatic adrenocortical cancer).