ACTA ENDOCRINOLOGICA (BUC)

Context. Neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) are recent prognostic markers associated with inflammation in many diseases such as chronic kidney disease (CKD), malignancies, myocardial infarction. Objective. In this study, we investigated the relationship between NLR-PLR and parathyroid hormone (PTH) and vitamin D in patients with high PTH levels. Design. The patients with high PTH levels in Nephrology and Endocrinolgy Outpatient clinics were evaluated retrospectively. Subjects and methods. The medical records of the patients were examined and clinical data, including demographic details, clinical and laboratory findings, treatment and follow-up data were obtained. NLR and PLR were calculated. Serum creatinine, calcium, phosphorus, magnesium, lipid levels, calcium phosphorus product, PTH and vitamin D values were investigated. The relationship between NLR-PLR and laboratory parameters, GFR (MDRD-GFR), PTH and vitamin D were investigated. Results. 48 male and 253 female patients were enrolled in this study. The mean age was 57.57±13.28. NLR correlated negatively with albumin, hemoglobin, vitamin D, calcium and cholesterol and it positively correlated with creatinine and PTH. Multiple regression analysis showed that main determinants of NLR were PTH, albumin, LDLcholesterol, hemoglobin and gender. Conclusions. In this study NLR and PLR correlated negatively with hemoglobin and cholesterol. Positive correlation between NLR and creatinine could be explained by increased degrees of inflammation associated with more pronounced degrees of renal dysfunction. The impact of PTH on NLR was independent of GFR. In multiple regression model this suggests that PTH could be a pro-inflammatory parameter independent of the degree of renal dysfunction.

Alteration in nervous system function in patients with thyrotoxicosis is frequent. In rare cases, mental disturbances may be severe: maniac-depressive, schizoid or paranoid reaction. The pathophysiologic basis of these nervous system findings is not well understood. The first patient, being on treatment with benzodiazepine and Risperidone for mood deterioration, was admitted in Thyroid Unit 1 for clinical features suggesting addition, he developed auditory and visual hallucinations, bizarre behavior, disorganized speech, disorientation, poor attention and loss memory for recent events, having a good clinical response after addition of antithyroid drug therapy. The second case developed clinical features suggesting thyrotoxicosis, associated with visual and auditory hallucinations, marked psychomotor agitation and bizarre behavior. After an unsuccessful monotherapy (Risperidone), a good response of clinical features (including psychiatric symptoms) to combined therapy (Methimazole and Risperidone) was recorded. The diagnosis of Graves’ disease was based on clinical and laboratory data (suppressed serum TSH level, elevated serum FT3) and ophthalmological examination or positive anti - TPO antibodies. Both patients were successfully treated with combined therapy - Methimazole and Risperidone. Both case reports demonstrate the importance of performing thyroid function tests in patients with acute psychosis.

Severe hypercalcemia is often caused by primary hyperparathyroidism (PHP), which is not commonly seen in patients with systemic lupus erythematosus (SLE). In this case report a 77 years old woman with a history of SLE develops mild hypercalcemia secondary to unrecognized PHP that leads to a hypercalcemic crisis with a prolonged recovery. Therefore, early diagnostic evaluation of persistent hypercalcemia in patients with SLE is important for detection and appropriate treatment of PHP to avoid a hypercalcemic crisis and associated prolonged morbidity.

Introduction. This case report is the fourth of its type in the medical literature. It describes total thyroidectomy for recurrent relapses of Graves encephalopathy (GE) despite medical treatment. Case presentation. A 33-year-old male presented with impaired consciousness and convulsions. He had postthyroid surgery recurrent Graves’ disease with a goitre. Based on this fact, high thyroid antibodies titres and the exclusion of other causes of such neurological manifestations, he was diagnosed to have GE. This is a rare variant of “encephalopathy associated with autoimmune thyroid disease” (EAATD). Despite the administration of steroid therapy and other standard therapeutic measures, he developed five relapses within 17 months. Total thyroidectomy was advised. Unfortunately, he got another severe attack that required intensive care admission. After three days of discharging, he had urgent total thyroidectomy. The operation went well and for 18 months’ follow-up he had no more attacks. However, thyroid antibodies remained high. Discussion. The report provides details on the diagnosis, standard management and the indication for thyroidectomy for GE. It describes its challenges, precautions, technique and outcomes. It reviews the extent of surgery as well as the clinical and antibody outcomes of the previous three related reports, in comparison with the current one. Conclusion. For medically uncontrolled relapse of GE, thyroidectomy consistently results in ending the attacks. It, therefore, should be put in more consideration in the treatment protocols. On the other hand, one should not depend on antibody levels as a measure of treatment success.

Introduction. Immune Dysregulation, Polyendocrinopathy, Enteropathy X-Linked (IPEX) Syndrome represents a rare X linked disorder, characterised by development of systemic autoimmunity from the first year of life. IPEX is due to mutations in the FOXP3 gene located on the X-chromosome. There are no specific laboratory tests to confirm the diagnosis. Molecular analysis of the FOXP3 gene(Xp11.2-q13.3) is required for the diagnosis. Chronic immunosuppression and hematopoietic stem cell transplantation represent the two main therapeutic interventions for this immune dysfunction, the last one being the only curative treatment. Case presentation. The authors present the case of a male patient aged 14 years old, who was admitted for ketoacidotic diabetes onset. He was diagnosed with polyendocrine autoimmune association (diabetes mellitus type 1, autoimmune thyroiditis and hypo-gonadotrophic hypogonadism). This patient associated celiac disease, sustained on clinical, immunological and histological changes:recurrent diarrhea, positive IgA anti-tissue transglutaminase antibodies and total villous atrophy on intestinal biopsy sample. He also presented recurrent eczematous dermatitis associated to elevated serum concentration of immunoglobulin E. The authors sustained the diagnosis of IPEX syndrome in this case based on family history of unexplained early deaths of the patient´s uncles from the motherside, along with clinical and laboratory aspects. Drug treatment included nutritional support, immunosuppressant therapy and hormone replacement. Conclusions. The most important aspect in this case was considering IPEX syndrome after integration of all clinical and paraclinical data but without molecular analysis of the FOX P3 gene. The presumption of IPEX syndrome reconsidered in this case the treatment and the prognosis. Life expectancy is reduced in this condition that usually occurs in the first months of life. The particularity of this case was the late onset of IPEX syndrome, presenting a severe phenotype with aggressive autoimmune associations that led finally to the patient’s death.

A 57 years old woman was diagnosed with welldifferentiated lung neuroendocrine tumor (NET) by laboratory assessment, computed tomography (CT), contrast-enhanced magnetic resonance imaging (MRI) and bronchoscophy with transbroncial biopsy of nodular lung lesion located in the right lower lobe. Staging Ga-68 positron emission tomography-CT (PET-CT) showed two pathological uptake regions in the superior segment of the right lung lower lobe (SUVmax: 80.61) and 6th thoracic vertebral body (SUVmax: 3.70). Contrast-enhanced MRI findings suggested that vertebral lesion may be compatible with atypical hemangioma or osseous metastasis due to T1 isointensity, T2 hyperintensity and contrast-enhancement on the lesion. Therefore, characteristic imaging findings of hemangioma were seen on axial and sagittal or coronal sections of CT, respectively called as ‘polka dot’ and ‘corduroy cloth’. Thus the mild vertebral Ga-68 DOTATATE uptake was accepted as false positive finding. Surgical intervention was decided. She underwent a right lung lobectomy. The last follow-up of the patient was done 2 years after the initial diagnosis. The follow-up Ga-68 DOTATATE PET-CT revealed no pathological increased uptake in the whole-body except the 6th vertebra showing similar uptake (SUVmax: 3.50) with the previous scan without size increase on CT. The patient was asymptomatic with normal serum chromogranin A level.

Context. The clinical presentation of histoplasmosis is varied. Due to its propensity for adrenal involvement, histoplasmosis is an important differential diagnosis in any patient presenting with adrenal mass, bilateral in particular. Objective. Data on clinical presentation, pattern of adrenal involvement, radiological appearance and long-term follow-up of adrenal histoplasmosis are relatively sparse; hence we looked at it. Design. This record based single-centre retrospective study was conducted in one of the tertiary care hospitals, situated in eastern India catering the Gangetic delta. Subjects and methods. Data on demographic characters, presenting manifestations, biochemical & hormonal parameters and radiological appearance of confirmed adrenal histoplasmosis cases (n=9), admitted between 2015-2019 have been retrieved. The treatment outcome and condition of patients after 1-4 years of followup has also been discussed. Results. Four out of the nine (44.4%) patients had predisposing immunocompromised conditions in the form of diabetes and/or chronic alcoholism while rest were immunocompetent. Seven out of nine patients (77.8 %) had signs and symptoms suggestive of adrenal insufficiency, while two (22.2%) presented with only pyrexia of unknown origin. All of them had bilateral adrenal mass, though the radiologically appearances were different. All patients received anti-fungal agents with/without hydrocortisone and/or fludrocortisone. One patient died (11.1%), while majority responded favourably to treatment. Adrenocortical function did not recover completely. Conclusions. The possibility of adrenal histoplasmosis should always be considered in patients presenting with bilateral adrenal mass, irrespective of adrenal morphology. Treatment is effective, but many of them require supplemental hydrocortisone for quite a long period, if not lifelong. Mineralocorticoid deficiency, however, is not permanent.

Introduction. The polyglandular autoimmune syndrome (PAS) type III is a rare condition defined as the coexistence of autoimmune thyroid disorder with other endocrine autoimmune diseases, including type 1 diabetes, without adrenal dysfunction. PAS may associate with other non-endocrine autoimmune diseases, overlapping with the multiple autoimmune syndromes (MAS). We present a case of PAS III/ MAS type 3, including autoimmune thyroiditis, autoimmune diabetes, vitiligo, lupus erythematosus, associated with adult-onset atopic dermatitis, a combination not reported previously. Case report. A 40 years old woman, registered as nurse working in dialysis unit, previously diagnosed with vitiligo, euthyroid autoimmune thyroiditis and disseminated granuloma annulare, with personal and familial history of atopic disorders, presented in our clinic for disseminated eczematous and lichenoid cutaneous rashes. She was tested positive for antinuclear, anti-double stranded DNA and anti-histone antibodies, with inflammatory syndrome and marginal lymphopenia and she was diagnosed with systemic lupus erythematosus (SLE). Subsequently, moderate hyperglycemia, positive anti-glutamic acid decarboxylase antibodies and low C-peptide level prompted the diagnosis of autoimmune diabetes. Recurrent flexural eczematous rashes, with negative epicutaneous tests but positive specific IgE tests for common allergens fulfilled the clinical criteria for the diagnosis of atopic dermatitis. The clinical, immunological and glycemic status were controlled with low doses of oral prednisone (<0.5 mg/kg), methotrexate (10mg/week), antimalarials, metformin, emollients and photoprotection. After changing her workplace, the immunosuppressive treatment could be discontinued, and the patient maintained normal immunological and biochemical profile at 6 months follow-up. This case brings a unique perspective on the evolution, associations spectrum and the management challenges of endocrine polyautoimmunity associated with atopic diathesis.

Introduction. Heart failure and dilated cardiomyopathy (DCM) in adults are rarely caused by hypoparathyroidism induced hypocalcemia. Case report. Female patient, 40 years old, diabetic, with previous history of thyroidectomy for Graves’ disease, was hospitalized for syncope and symptoms of heart failure. ECG revealed sinus tachycardia, long QT, negative T from V1 up to V4. Chest X-ray, cardiac ultrasound and contrast cardiac MRI confirmed dilated left chambers, severe systolic dysfunction of the left ventricle (left ventricle ejection fraction=15%) due to diffuse hypokinesia and restrictive type of diastolic dysfunction. Patient status insignificantly improved with specific heart failure depletion treatment but important signs of hypocalcemia occurred. Low levels of total and ionic serum calcium were detected (total serum calcium 3.6 mg/dL, ionic calcium=2.2 mg/dL) along with low serum levels of parathormone (10 pg/mL) and high level of phosphatemia (6.4 mg/dL). After one month of parenteral treatment with calcium and oral vitamin D, hypocalcemic signs disappeared and heart failure significantly improved. Conclusion. This rare adult condition is refractory to heart failure conventional therapy but promptly responds to restoration of normocalcemia. It is important to be aware of this pathophysiological setting, in order to treat it correctly.

Introduction. Prader-Willi syndrome (PWS) is one of the most common known genetic causes of morbidly obese, resulting in\r\ndiabetes mellitus (DM) and the management of DM in PWS is difficult. Recently, glucagon-like peptide 1 (GLP-1) receptor agonists have been introduced for the treatment of type 2 DM. Here, we report the use of liraglutide, a GLP-1 receptor agonist, in a patient with DM in PWS.\r\nCase report. A Japanese male patient was diagnosed as having PWS at the age of 1 year. He was mentally retarted and developed morbid obesity. When he was 18 years old, his\r\nweight was 79 kg and height was 152 cm (BMI 34.1 kg/m2). His HbA1c level was 6.2 % and thus DM was diagnosed. Despite\r\nseveral medications, the control of DM worsened and thus at the age of 22 years his body weight and HbA1c further increased (83 kg and 10.8%, respectively). At this time,\r\nliraglutide was initiated. His weight and BMI did not change, however his HbA1c level decreased to 7.4 % after one year treatment. He did not have any side effects of liraglutide. This case indicates that GLP-1 receptor\r\nagonists may be useful for the treatment of DM with PWS.