ACTA ENDOCRINOLOGICA (BUC)

Context. Acromegaly, a severe condition characterized by excessive and unmodulated secretion of growth hormone, leads to morphologic disturbances and multisystem complications. Objective. The purpose of this study was to evaluate the quality of life (QOL) in patients with acromegaly compared to matched obese patients. Design. This was an observational cross-sectional study. Subjects and methods. We enrolled 49 patients with acromegaly and 49 obese patients. AcroQoL (acromegaly QoL questionnaire) was applied to all patients and IGF-1 (type 1 insulin-like growth factor 1) was measured. Results. Patients with acromegaly had a worse QoL compared to patients with obesity (score= 77(53-86) vs. 96(90- 102), p˂0.001). In the group of patients with acromegaly, there was no difference in the QoL regarding the activity of the disease (active, controlled, or cured). Men had a higher AcroQoL score than women (score= 88(55-95) vs. 74(52.75- 82), p=0.02), but there was no difference between patients with microadenomas and the ones with macroadenomas (score= 82(66-88.5) vs. 73(55-83), p=0.136). The most frequent complications were cardiovascular complications (81.63%), articular complications (73.46%), dyslipidemia (65.30%) and digestive complications (63.26%). Conclusions. Despite complex treatment and hormonal control, the presence of complications reduces the quality of life in patients with acromegaly, even when compared with obese patients.

Introduction. First election treatment in Cushing’s syndrome is the surgical therapy (pituitary or adrenal). Pharmacotherapy is used: before surgery, when the surgery was ineffective, in association with radiotherapy or in cases of refuse or contraindications for surgery. Aim of the study. Testing the effectiveness and safety of Ketoconazole treatment in patients with Cushing’s syndrome. Methods. We studied 12 patients with Cushing’s syndrome treated with Ketoconazole between 2010 and 2013. We followed cortisol levels before and during treatment, the doses of Ketoconazole and the time required for normalization of cortisol, “the escape syndrome” and the adverse effects. Results. Eleven (91,66%) patients had ACTH – dependent Cushing’s syndrome. The mean basal cortisol before initiation of the therapy was 404.4 ± 71 ng/ml. Two thirds (eight) patients presented a normalization of serum cortisol levels with 300-800 mg Ketoconazole/day, during a mean of 8.5 weeks. Only one patient presented an “escape syndrome” and one presented adrenal insufficiency. None of the patients showed significant side effects under the treatment. Conclusions. Ketoconazole therapy is well tolerated and is effective in most patients with Cushing’s syndrome even in long term use. The resistance and the escape from the effect of the treatment is possible, but rare, patients requiring close monitoring during therapy.

Hypothyroidism is a frequently diagnosed endocrine disorder that has characteristic\r\nclinical signs and symptoms. The frequency of myopathy in hypothyroidism ranges from 30 to\r\n80%. The major symptoms related are: weakness, muscular cramps and myalgia. The\r\npseudohypertrophic form is called Hoffman's syndrome and is quite rare, reassign diagnosis\r\ndifficulties both to endocrinologists and neurologists. The pathogenesis of this form of\r\nmyopathy is still unclear. We report the case of two patients, daughter and father with\r\npseudohypertrophic myopathy and hypothyroidism by Hashimoto's thyroiditis. The two were\r\npreviously treated for hyperthyroidism: first by antithyroid drugs and secondary by surgery (the\r\ndaughter) and radioiodine (the father). Both developed iatrogenic hypothyroidism that vas\r\ntreated by thyroxin replacement therapy. The muscular symptoms: progressive proximal\r\nweakness, muscle hypertrophy accompanied by stiffness, spontaneous muscular pain, muscular\r\ncramps and fatigue during mild exercise have developed during the year before admittance. In\r\nboth patients Hashimoto's thyroiditis was revealed by the high level of TPO antibodies and the\r\nthyroid appearance in sonography. Hormonal dosages confirmed hypothyroidism. Elevated\r\nvalues of CPK and electromyography established the diagnosis of thyroid myopathy. Muscular\r\nsymptoms were improved but not remitted by the thyroxin replacement therapy in adequate\r\ndoses, but CPK normalized. It is the first time that a familial case of Hoffmann syndrome is\r\ndescribed, suggesting a genetic susceptibility to the development of the syndrome.

Introduction. McCune-Albright syndrome (MAS) is a noninherited, genetic condition defined by the clinical triad: polyostotic fibrous dysplasia (FD), café-aulait skin spots and different hyper functioning endocrinopathies. Case presentation. The patient, a 39-year-old female previously diagnosed with MAS, presented with severe, left-sided skeletal pain and accentuated asymmetrical facial features. Although there were no clinical signs (except type II diabetes) the hormonal dosages revealed GH hypersecretion and ACTH-independent hypercortisolism. The modified bone anatomy rendered the surgical adenomectomy impossible, whereas radiotherapy was not an option due to the increased risk of sarcomatous transformation of FD; therefore somatostatin analogues were used. Cushing syndrome was cured by left adrenalectomy. For the facial dysmorphism, surgical cure was proposed. CT revealed a pituitary microadenoma, severe craniofacial hyperostosis and left-side macronodular adrenal hyperplasia. Conclusion. We report the case of an adult female with MAS associating both acromegaly and Cushing syndrome, the MAS-Cushing syndrome association having been identified only in children up to present. The setting of a therapeutic strategy in these cases is difficult determined by the multiple concomitant tissue damage and by the limited number of therapeutic options available, not only for acromegaly, but also for pain management and the cure of bone deformities.

Introduction. Subtypes of nonfunctioning pituitary adenomas which may differentiate into functioning adenomas are silent corticotroph adenomas (SCA). These are pituitary tumors positive on immunohistochemical staining for ACTH, but without clinical evidence of Cushing’s disease. Case report. FG, a 50 years old man was twice operated for compressive non secreting pituitary macroadenoma (NFPA). After the first surgery he developed hypopituitarism and needed replacement therapy for all the hormonal lines. After the second surgery he rapidly developed the clinical features of Cushing’s syndrome. Hormonal dosages showed: the absence of the circadian rhythm of cortisol, high ACTH level and the lack of suppression at 1 mg overnight and high dose Dexamethasone suppression tests. The immunohistochemistry of the previously resected pieces confirmed the diagnosis of a silent corticotroph adenoma. The patient was referred for conventional antitumoral radiotherapy associated with Cabergoline, then with Ketoconazole treatment. As the high levels of cortisol recurred, he was subjected to bilateral adrenalectomy. Conclusions. We present the rare case of a silent corticotroph macroadenoma which became hypersecreting after two pituitary adenomectomies. SCA may represent another entity in the spectrum of Cushing’s syndrome that must be evoked in the cases of pituitary macroadenomas thought to be non-functional.

This editorial discusses the context of thediscovery of GNRH 1 as a cause of congenital hypogonadotropic hypogonadism published last year by Bouligand et al in the New England Journal of Medicine

Background. Virilizing syndrome in a postmenopausal woman is a concerning matter, raising the suspicion of androgen-secreting tumour. Case report. A 65 years old woman presented with severe virilization features evolving rapidly over 4 years, accompanied by: severe polyglobulia, severe hypertension, dyslipidemia and uterine fibromatosis compressing both ureters, producing first degree hydroureteronephrosis. The hormonal dosages showed very high levels of both testosterone (15.5 ng/mL) and estradiol (299 pg/mL), meanwhile DHEAS level was normal, indicating an ovarian pathological secretion. The endovaginal ultrasound and computed tomography scan revealed an enlarged right ovary of 5.5/2.8 cm. A total hysterectomy and bilateral oophorectomy was performed. Pathological examination confirmed the diagnosis of right ovarian hilum Leydig cell tumour. After surgery, the testosterone and estradiol levels normalized (concordant to the age and menopausal status), the virilizing syndrome progressively improved and polyglobulia, hypertension and dyslipidemia remitted showing their secondary etiology. Conclusion. We present a very rare case of secreting ovarian Leydig cell tumour in a postmenopausal woman, showing besides the virilizing syndrome, four unusual features: severe polyglobulia, due to androgen excess, severe hypertension and dyslipidemia, all remitted after tumour removal, and severe compressive uterine fibromatosis that was the consequence of the estrogen excess.

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. In our department the standard surgical procedure for multinodular\r\ngoiter used to be subtotal resection. Over the years, total thyroidectomy has progressively\r\nreplaced subtotal resections and is performed in most of our patients at present.\r\nPatients and Methods. In a prospective cohort, observational study, we assessed\r\nthe immediate surgical outcome in 742 consecutive patients with multinodular goiter\r\n(MNG), admitted for surgery and operated in our hospital. Of all patients, 664 were women\r\n(89.5%) and 78 men (11.5%), aged 15 to 85 years, mean (?SD) of 48 ?13.8 years. Pathology\r\nwas done on frozen and permanent sections. The complications directly related to surgery\r\nin subtotal thyroidectomy (STT) were compared to total thyroidectomy (TT) or near-total\r\nthyroidectomy (NTT) patients: temporary hypoparathyroidism, temporary RLN injury,\r\npermanent hypoparathyroidism and permanent RLN injury. The &#967;2 test (95% confidence\r\ninterval) was used and values of p<0.05 were considered significant.\r\nResults. There were no significant differences among the patients with SST for\r\nMNG, NTT or TT , and TT for recurrent MNG or completion thyroidectomy, with respect\r\nto temporary and permanent RLN injury. Significant differences were found for temporary\r\nhypoparathyroidism in STT for MNG (9 out of 361 patients, 2.45%) and NTT or TT for\r\nMNG (21 out of 266 cases, 7.89%) (p<0.01) and between STT for MNG (9 out of 361 cases,\r\n2.45%) and TT for recurrent MNG for completion thyroidectomy (8 out of 45 cases,\r\n17.77%) (p<0.01) and no difference between NTT or TT for MNG (21 out of 266 cases,\r\n7.89%) and TT for recurrent MNG or completion thyroidectomy (8 out of 45 cases, 17.77%)\r\n(p=0.11). We registered no permanent hypoparathyroidism in our patients.\r\nConclusions. Total thyroidectomy is now the preferred option for the management\r\nof patients with bilateral benign MNG. However, TT is associated with a considerable rate\r\nof complications, higher than of STT. In patients with bilateral MNG and no malignancy,\r\nSTT remains in our opinion, a valuable option.

Background. ROHHADNET syndrome is a pleiotropic disorder defined by rapid onset of obesity, hypothalamic-pituitary endocrine dysfunctions, alveolar hypoventilation and hypothalamic autonomic dysregulation and neural tumors. Case presentation. We report the case of a 5.8-year-old female patient with rapid onset of obesity and growth arrest, hypercortisolism, hyperprolactinemia, low IGF1, severe hypernatremia (with no signs of diabetes insipidus) and chronic hyperchloremic metabolic acidosis. Additional symptoms included sleep apnea and two episodes of cardiopulmonary arrest after mild sedation. Brain MRI, chest and abdominal enhanced CT scans were all negative. As no tumors were revealed at the time of diagnosis, ROHHAD syndrome was suspected. Treatment with potassium bicarbonate was initiated in an attempt to control both the severe hypernatremia and chronic hyperchloremic metabolic acidosis. Patient developed dilated cardiomyopathy and kaliopenic nephropathy. Conclusion. The presence of dilated cardiomyopathy is in keeping with only one other reported case, while the severe hypernatremia joined by hyperchloremic metabolic acidosis seen in our patient has not been presented previously. Although it is a very rare medical condition, ROHHAD syndrome has to be considered in the differential diagnosis of any case with rapid onset obesity associated with hypothalamic-pituitary endocrine dysfunctions, and alveolar hypoventilation.