ACTA ENDOCRINOLOGICA (BUC)

The appearance and normal development of the anterior pituitary gland requires several signalling molecules and specific transcription factors. Gene mutations of these\r\npituitary transcription factors may lead to different degrees of combined pituitary hormone deficiency (CPHD) associated or not with morphological changes of the hypothalamicpituitary region. We present the first Romanian case of progressive CPHD in two brothers from a consanguineous family. Clinical, hormonal and MRI follow-up were performed during 20 years. Growth hormone deficiency was certified at the age of 5, respectively 3 years, followed by gonadotropin deficiency diagnosed at the age of 21, respectively 19 years, and by central hypothyroidism diagnosed at the age of 23, respectively 21 years.\r\nSubstitutive treatment rhGH was commenced, followed by testosterone and later thyroxin, in adequate doses. Adrenal function was normal during the follow-up. MRI revealed\r\nanterior pituitary hypoplasia in both siblings, with a partially empty sella in the younger brother and a thick midline septum in the sphenoid sinus in both siblings, which was not described in previous reports. The progressive CPHD suggested a PROP 1 deficiency, which was confirmed by genetic analysis. The c.301-302delAG homozygous mutation in the PROP 1 gene was identified, resulting in a complete loss of promoter binding and\r\ntranscriptional activation of the mutant protein.

Introduction. Autoimmunity derives from a complex interplay of genetic and environmental factors. Major histocompatibility complex (MHC) alleles and non-MHC loci have been identified as susceptibility markers. Few studies evidenced an association between autoimmune thyroid disease (ATD) and CT60 or 49 A/G polymorphisms in the CTLA-4 gene. Objectives. The aim of our research was to investigate in a pilot case-control study whether other two CTLA-4 gene polymorphisms, i.e. the CTLA-4 1661 A/G and the CTLA-4 658 C/T single nucleotide polymorphisms (SNP), are involved in genetic predisposition to ATD. Material and methods. Between January and April 2009, 42 subjects entered the study. Of these, ATD (i.e. chronic autoimmune thyroiditis, Graves’ disease) was diagnosed in 21 patients, whereas in 21 subjects no signs of autoimmunity were identified. CTLA-4 gene polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results. No association was observed between the CTLA-4 1661A/G gene polymorphism in patients with ATD and controls (p = 0.094, by chi-square test). Likewise, no statistically significant difference was noticed between groups with regard to the CTLA-4 658 C/T gene polymorphism (p = 0.649). Conclusions. At the time being, this is the first case-control study that examined and demonstrated lack of association between CTLA-4 -1661 A\G and -658 C\T SNP and ATD; however, larger numbers of subjects are needed to clarify the role of CTLA-4 gene polymorphisms in endocrine autoimmunity.

Introduction: During the past thirty years bone biopsy has been used as an invasive diagnostic and research investigation of bone structure and metabolism. Quantitative bone histomorphometry parameters offer information on both bone mass and bone quality.\r\nObjectives: This study aimed to establish the value of routine qualitative bone biopsy evaluation in subjects with unexplained primary osteoporosis. Patients in whom low bone mineral density was not adequately explained by risk factors or patients in whom therapy\r\nwas not followed by BMD changes according to evidence-based data on treatment of osteoporosis were referred to bone biopsy. One-hundred seventy patients (73 men and 97 women), aged 54.29?0.95 years, were included in the study. The diagnosis was based on clinical data, lumbar spine and hip dual X-ray absorptiometry (DXA) evaluation and routine laboratory measurements. Bone biopsy was performed by horizontal approach, using an electric drill. Qualitative bone biopsy evaluation was performed in one single department by trained pathologists. Quantitative bone histology assessment (histomorphometry) was not available.\r\nResults: Of the 170 bone samples, secondary causes of low bone mineral density were identified in 19 patients (mastocytosis, multiple myeloma, myeloproliferative syndrome, sarcoidosis and osteomalacia). In 21 subjects with osteoporosis as defined by WHO criteria qualitative histological evaluation found no pathological changes. Accelerated bone resorption as expressed by the daily urinary levels of deoxypyridinoline (D-Pyr) and longterm sodium fluoride therapy were associated with relevant osteoidosis as assessed by qualitative evaluation of bone samples. Bone biopsy changes were not related to serum thyroid hormone, parathyroid hormone or 25-hydroxyvitamin D3 levels.\r\nConclusions: Qualitative bone biopsy evaluation may offer valuable information in the diagnosis of metabolic bone diseases in subjects with unexplained causes of low bone mineral density or in non-responders to anti-fracture agents. Despite of lack of quantitative information on bone mass and the degree of mineralization of bone tissue, few patients with osteoporosis may benefit from this diagnostic routine procedure.

Graves’ disease is an autoimmune disorder characterized by various degrees of thyroid gland, eye and skin affection. We present the case of a 36 years old woman diagnosed with Graves’ disease and infiltrative ophthalmopathy class IV according to Werner classification, non-responsive to Methylprednisolone antiinflammatory therapy and to irradiation. From anamnesis we mention Graves’ disease’s debut approximately one year ago, manifested by thyrotoxicosis features without evident ophthalmopathy. Antithyroid drug therapy was started at debut and maintained for eleven months. One month after antithyroid drug therapy cessation, the patient developed diplopia, periorbital edema, and proptosis. At that moment we decided to initiate intravenous Methylprednisolone therapy using a total dose of 3 grams, followed by oral corticotherapy in association with antithyroid drug therapy. One month later, when bilateral fat tissue hernia appeared in the external orbital angle, we decided to add orbital radiotherapy. In the absence of any evident clinical improvement, immunosuppressive treatment with Cyclosporine 5 mg/kg/day was chosen. Consequently, ,we obtained a significant reduction of eye proptosis, 4 mm at the right eye, and 3 mm at the left eye, a significant reduction of bilateral orbital fat tissue hernia, and no more diplopia.

Anorchia is a syndrome characterized by unilateral or bilateral absence of testicular tissue.\r\nAt puberty, growth and development are normal but secondary sexual development fails to\r\noccur if anorchia is bilateral.\r\nWe present the case of a 21 year-old male with a late diagnosis of bilateral anorchia. The\r\ndiagnosis was suggested by a bilateral empty scrotum, in a patient with male phenotype and\r\npoor secondary sexual development and established by karyotype analysis, hormonal profile\r\nand surgical exploration. The lack of testosterone response to hCG stimulation is the hormonal\r\nhallmark of bilateral congenital anorchia. In the absence of any information about germinal cell\r\npresence, bilateral excision of the testicular nubbins, implantation of testicular prostheses and\r\nhormonal replacement therapy were indicated.

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