ACTA ENDOCRINOLOGICA (BUC)

Background. An adrenal collision tumor is a rare entity. We present a rare combination of giant adrenal ganglioneuroma (GN) and myelolipoma. GN is a rare benign tumor of the adrenal medulla that originates from primitive neural crest cells, while myelolipoma is a benign tumor of the adrenal cortex comprising of mature adipose tissue and blood components. Case Report. We present a case of a 52-year-old male who presented with generalized body swelling with episodes of vomiting and diarrhea. There was no history of abdominal pain or any significant history. Routine laboratory investigations and endocrine workup were within normal limits. MRI was performed for unexplained symptoms, and which revealed a solid homogeneous mass measuring 9x7x4.5cm arising from the adrenal gland. A diagnosis of myxoid adrenocortical neoplasm was suggested, and laparoscopic left adrenalectomy was performed based on imaging findings. The final diagnosis of coexisting giant adrenal GN with myelolipoma was made on histopathological examination, which was further confirmed by immunohistochemistry. Conclusion. Ganglioneuroma coexistence with myelolipoma is a rare finding in the adrenal gland. Therefore, histopathology is imperative in such cases for a definitive diagnosis.

Zygomycosis is a frequently fatal infection in the immunocompromised and diabetic host. A 12 year old girl with type 1 diabetes presented in diabetic ketoacidosis and consolidation of right lung along with thymic abscess causing persistent respiratory symptoms. A diagnosis of\r\nmucormycosis was made on smear examination of the thymic aspirate. Intravenous amphotericin along with surgical excision of the abscess resulted in clinical cure. Thymic involvement as seen in this case is an extremely rare occurrence in a diabetic patient which has not been\r\nreported in literature so far .

Context. Propylthiouracil (PTU) could cause lupus or vasculitis-like hypersensitivities thus interfering with some other concomitant diseases. Objective. Clinicians must be aware of the side effects of medications, particularly after their introduction and long-term use. Some clinical manifestations may be similar to well-known drug side effects or hypersensitivity. Every unusual clinical scenario related to drug use must be evaluated individually and thoroughly. Subjects and Methods. Hands and feet skin changes were observed several days after PTU administration in a male patient with severe diffuse toxic goitre. A complete blood count, biochemistry analyses, thyroid function tests and antibodies, and immunology analyses were performed. Results. As the skin changes were distributed regionally, liver function tests were normal, and there were no signs of clinical deterioration, it was decided to continue PTU treatment and monitor the patient. The initial maculopapular rash quickly turned vesicular, then scaly. After two weeks, the skin changes were wholly restored, with no scarring. Hand, Foot, and Mouth disease (HFMD) was diagnosed after a thorough epidemiological survey and clinical workout. Conclusions. Our case study demonstrates that skin changes associated with HFMD may resemble those associated with PTU-induced vasculitis.

A 5 year 2 months old boy was admitted in our hospital for failure to thrive, muscle weakness, bowing of legs, walking difficulties. At the age of 14 months he had been investigated for failure to thrive. Clinical, biochemical and radiologic signs were suggestive for rickets. Positive celiac serology and histology of the small bowel were consistent with the diagnosis of celiac disease (CD). Treatment included parenteral vitamin D and gluten free diet. The parents did not accept the diet, but the child received a daily vitamin D supplementation of 1000 IU. At the age of 4 years celiac serology was positive and the second duodenal biopsy was normal. \r\nPhysical examination, biochemical data, and rachitic changes on x-ray were compatible with the diagnosis of rickets. Clinically severe rickets, hypocalcemia, elevated level of PTH demonstrating secondary hyperparathyroidism, and low level of calcitriol determined the diagnosis of vitamin D-dependent rickets type I (VDDR I). Although being on a normal diet, tissue antitransglutaminase antibodies were negative, but HLA genotyping showed DQ2 positive. \r\nThe patient associated the diagnosis of VDDR I and latent CD. The VDDR I was masked by CD, rickets being attributed to malabsorption.

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.

Context. Adrenocortical carcinoma (ACC) is a rare neoplasm with an aggressive course and poor prognosis. The worldwide incidence is about 0.5 to 2 cases per million population per year. Oncocytic adrenocortical carcinoma is a rare histopathological variant of ACC with only a few reported cases in the literature. Case report. We report a case of an oncocytic variant of adrenocortical carcinoma in a 21-year-old male patient who presented with a left adrenal mass. Imaging studies confirmed a large left adrenal mass with involvement of the left renal vein and inferior vena cava. Endocrine workup showed mildly elevated serum cortisol levels. Discussion. Oncocytic AAC is a rare histopathological variant of ACC, as well as a rare subgroup of oncocytic adrenal neoplasms Hormonally active or functioning adrenocortical carcinomas most commonly secrete cortisol whereas co-secretion of multiple steroid hormones is a rare phenomenon. Conclusions. Surgery remains the mainstay of treatment, but most of the patients present late with large masses and eventually become unsuitable for curative resection.

Hyperinsulinism/hyperammonemia (HI/HA) syndrome is caused by activating mutations in GLUD1 gene, and causes fasting as well as protein sensitive symptomatic hypoglycemia, in addition to persistently elevated plasma ammonia levels. First-line treatment is diazoxide, and most patients respond well to this agent, however side effects may be observed. The most frequent side effect of diazoxide is fluid retention and hypertrichosis, while hyperuricemia and hematologic side effects are observed less often. Herein, we report a case who had a heterozygous mutation of GLUD1 gene and who developed diazoxide related neutropenia 8 years after the start of treatment. On follow-up, leucopenia and mild neutropenia persisted and the treatment was changed to somatostatin analogues. However, she developed persistent severe symptomatic hypoglycemia and required diazoxide retreatment. A lower dose of diazoxide (6 mg/kg/day) successfully controlled hypoglycemia and cell counts increased even though they were not normalized. Neutropenia in current case presented after a long period of time of diazoxide use and this period is the longest defined in the literature. Long-term endocrine and hematologic follow-up of this patient up to 18 years old will also be presented.

As the medical utility of injectable therapeutic peptides is expanding, so is the challenge of developing technologies that allow the administration of such molecules via alternative routes, considering that chronic patients requiring treatment with parenteral formulations are less adherent and compliant to the therapeutic regimens. Hence, substantial efforts have been made to develop technologies that allow the oral formulation of peptides. Due to their importance in the field of pharmaceutical technology, we describe the latest advancements made in the development of oral salmon calcitonin and oral semaglutide, in co-formulation with absorption enhancers such as 8-[(5-chloro-2-hydroxybenzoyl) amino] octanoic acid (or 5-CNAC) and N-[8-(2-hydroxybenzoyl) amino] caprylate (or SNAC). Oral semaglutide is considered to be a landmark for oral peptide delivery technology, as it is one of the very few successful examples of peptides that can be administered orally. Unlike semaglutide, oral calcitonin is still not approved by the regulatory authorities because it failed to demonstrate the anticipated effects in phase III clinical trials conducted so far. However, the efforts for obtaining an oral form of calcitonin have significantly contributed to the development of technologies that facilitate the absorption of peptide-structure macromolecules.

Background. Polycystic ovarian syndrome (PCOS) involves various changes within folliculogenesis. Aside from its systemic action, metformin seems to exert a local direct effect independent of insulinemia. The IGF system appears to be an important local target for metformin although the evidence we possess is circumstantial. Objective. The aim of this study was to evaluate the impact of metformin on insulin growth factor (IGF) system proteins and steroids production in PCOS patients and to analyze potential involvement in oocyte quality. Material and methods. This prospective study was performed on 86 in vitro fertilization (IVF) patients who were categorized into three groups as follows: Group 1 formed of PCOS patients who received metformin (n=27); Group 2 with PCOS patients who did not receive metformin (n=29) and Group 3 with controls (n=30). Interventions. Interventions included controlled ovarian stimulation for IVF and metformin (at least 16 weeks prior to the time of ovarian puncture). Main Outcome Measures.Follicular fluid analysis was performed using radioimmunoassay with specific kits (estradiol, testosterone, progesterone, IGF I, IGF II, IGF binding protein 1 - IGFBP1, IGFBP2, IGFBP3, IGFBP4). Results. Important differences were measured for the three types of steroids among the three studied groups (PCOS treated, PCOS not treated, controls) estradiol (538 vs. 466 vs. 688 ng/mL p < 0.0001), testosterone (6.7 vs. 7.6 vs. 5.1 ng/mL p<0.01), progesterone (8899 vs. 7878 vs. 9755 pg/mL p<0.0001) while for IGF system proteins important differences were noted only regarding IGFBP1 (114 vs. 107 vs. 121 p<0.002) IGFBP2 (263 vs. 268 vs. 252 ng/mL p<0.04), and IGFBP4 (128 vs. 138 vs. 118 p<0001). Correlations were also established between fertilization rate and estradiol (R: 0.53 p<0.5), testosterone (R: -0.39 p<0.05), IGFBP1 (R: 0.48 p< 0.05), IGFBP4 (R: 0.39, p<0.05). Conclusions. Patients with PCOS and hyperinsulinemia have the greatest benefit from metformin treatment. However, metformin action surpasses correction of systemic differences having a direct action at the level of follicular structures. Alteration of IGF system proteins does not concern only hyperinsulinic patients and can be partially amended by metformin administration.