ACTA ENDOCRINOLOGICA (BUC)

Objective: Co-existence of Cushing disease and Rathke?s Cleft Cyst (RCC) has been reported in a few cases in the literature so far. We herein describe a rare condition of Cushing disease that might originate from epithelium of RCC. \r\nCase: A 48-year-old woman was admitted to the hospital with complaints of headache, weakness, and weight gain. The patient underwent endoscopic transsphenoidal surgery due to Cushing Disease. Histopathological examination revealed cyst contents and walls compatible with RCC, and normal adenohypophysis and neurohypophysis tissues. Immunhistochemical staining with ACTH, GH, and prolactin were positive on the epithelium of the cyst. \r\nConclusion: In our case Cushing disease might be associated with hormonal activity derived from cyst wall of RCC or disappearance of a small microadenoma during surgical or pathological processing. According to recent data, origin of this lesion and histogenetic link between RCC with Cushing disease could not be explained.

Thyroid tumors are the most frequently reported endocrine malignancies. However thyroid collision tumors are rare pathological findings, representing less than 1% of thyroid cancers. In our case, a 50-year-old female patient presented with a complaint of neck swelling. During the exams, nodules were identified in both thyroid lobes. Pathologic analysis of a fine-needle aspiration biopsy(FNA) has been obtained from a 60×50 mm hypoechoic nodule raised suspicion of oncocytic carcinoma(OC). Another FNA was performed on a 17×11 mm hypoechoic solid nodule, revealing features of medullary thyroid carcinoma (MTC). Preoperative whole-body scans indicated no evidence of metastases. The patient subsequently underwent total thyroidectomy and central lymph node dissection. Pathological examination revealed OC, MTC, papillary microcarcinoma (PTMC), simultaneous metastasis of MTC and papillary thyroid carcinoma (PTC) to the same lymph node. The patient's calcitonin level was normalized postoperatively and I-131 ablation therapy was administered to the patient in the ATA high risk category. The patient was monitored under levothyroxine suppression. The simultaneous occurrence of OC, MTC and PTMC of the thyroid gland along with metastases of PTC and MTC in the same lymph node are reported in this case. To the best of our knowledge, this association had not been previously reported in the literature.

Context. The metabolic effects of primary hyperparathyroidism (PHPT) causing increased cardiovascular morbidity have begun to gain importance in medical science, and the number of studies investigating glucose metabolism disorders in asymptomatic PHPT patients is rare. Objective. To evaluate the relationship between glucose metabolism disorders and calcium, phosphorus and parathyroid hormone concentrations in asymptomatic PHPT patients. Subjects and Methods. Fifty-five asymptomatic PHPT patients were included into the study. Control group consisted of 55 normocalcemic cases. Oral glucose tolerance test (OGTT) of 75 g was performed with patients and controls. Insulin resistance was calculated by HOMA index. Results. No significant difference was present between groups regarding fasting plasma glucose, basal insulin and HOMA levels. Glucose levels measured at minutes 30, 90 and 120 after OGTT were higher in patients than in controls (p=0.041, p=0.025 and p=0.001, respectively). No individuals in both groups were diagnosed with diabetes mellitus. While impaired glucose tolerance was detected in six patients with asymptomatic PHPT, no impaired glucose tolerance was determined in controls. A positive correlation was found between serum calcium levels, and fasting plasma glucose and OGTT glucose levels were measured at minutes 60, 90 and 120. Mean fasting plasma glucose was significantly higher in patients with serum calcium levels ≥ 10.5 mg/dL than those with serum calcium levels <10.5 mg/dL (p=0.008). No significant correlation was detected between serum phosphorus and parathyroid hormone levels, and glucose levels were determined in OGTT and HOMA index. Conclusion. Increased levels of serum calcium affect glucose metabolism, so leading to glucose intolerance.

Context. Immunoassays are vulnerable to occasional analytical errors despite their sensitivity and specificity. Adrenocorticotropic hormone (ACTH) is among hormones which are vulnerable to assay interference. Objective. In this case report, we aimed to present a case of ACTH interference in a patient with subclinical hypercortisolism. Case report. We present a case of subclinical hypercortisolism with unexpectedly elevated levels of ACTH in whom interference was shown by different biochemical methods. It is important for the clinician to keep in mind the possibility of interference when clinical and laboratory results are discordant. The communication between the clinician and laboratory staff is important while interpreting results. This case report shows that ACTH interference should be considered in patients with subclinical hypercortisolism who have unexpectedly high levels of adrenocorticotropic hormone.

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 .

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.

Triple A syndrome is an autosomal recessive inherited multisystem disorder that was first described in 1978. Triple A syndrome has a high genotypic and phenotypic heterogeneity and has been linked with mutations in the AAAS gene, which has been identified on chromosome 12q13. A 14 years old male patient applied to outpatient clinic complaining of weakness and darkening of skin color since 4 months. On physical examination hyperpigmentation was observed on both the skin and mucosa. The morning cortisol level was 1.8 μg/dL and ACTH was >1250 ng/L. Schirmer test showed absence of tears. In the patient’s esophagoscopy, mucosal paleness and stenosis of the cardia were observed. Molecular genetic analysis of AAAS gene confirmed the diagnosis of triple A syndrome caused by homozygous mutation: c.1368_1372delGCTCA (p.Gln456HisfsTer38). This variant is considered to be a possible pathogenic because it causes a frame shift that changes the protein structure. As a result of the genetic analysis of the patient’s parents, the AAAS gene was detected as heterozygous in both parents for the c.1368_1372delGCTCA mutation. To the best of our knowledge, this is the first report of homozygous mutation: c.1368_1372delGCTCA (p.Gln456HisfsTer38).

A 52-year old women was diagnosed with acromegaly 5 years ago, and transseptal transsphenoidal pituitary microsurgery has been performed. Later the patient did not come to controls and the complaints prior to operation growth of the hands and feet, headache, sweating and resistant hypertension have continued. She was referred to our clinic with the same complaints. Physical examination showed typical acromegalic features without typical Cushingoid features. Magnetic resonance imaging of the brain revealed the presence of a pituitary macroadenoma. Basal plasma levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels were high. GH suppression was not observed in 75 gr oral glucose suppression test. Due to refractory hypertension and central obesity hypothalamo-pituitaryadrenal (HPA) axis was evaluated. HPA showed a lack of circadian rhythm of adrenocorticotropic hormone (ACTH) and cortisol, non-suppressibility to 1 mg overnight and classical 2 day low-dose dexamethasone, but suppressibility to high-dose (8 mg) dexamethasone. The tumour resected by transsphenodial surgery was histopathologically consistent with the diagnosis of adenoma. Immunostaining showed GH and ACTH producing cells. After surgery plasma GH and IGF-1 levels decreased to normal along with normalization of HPA axis. Hypertension disappeared without medical treatment after removal of the pituitary tumour. This is a very rare case of GH-producing pituitary adenoma causing typical acromegaly with concomitant production of ACTH causing subclinical Cushing’s disease.

Introduction. Irisin is a recently discovered novel adipomyokine that induces an increase in total body energy expenditure, improves insulin sensitivity and glucose tolerance. It has been shown that circulating levels of irisin are low in patients with obesity, diabetes mellitus and impaired glucose tolerance. However, the information about the level of circulating irisin in gestational diabetes mellitus (GDM) is controversial. Material and Methods. Serum irisin was measured by an ELISA in a longitudinal prospective cohort study in 221 women. There were 156 healthy pregnant and 65 women with GDM. Results. Circulating irisin levels were significantlly higher in the middle pregnancy compared with early pregnancy levels in healthy pregnant women and in women with GDM. Serum irisin levels were found to be lower in GDM compared to healthy pregnant women during first trimester but the difference was not observed throughout the pregnancy and it was comparable in middle pregnancy. There was a significant inverse correlation of BMI with serum irisin (r = -0.193, p = 0.004) and between HbA1c and mean glucose of OGTT with serum irisin (r =-0.377, p =0.0001) and (r = -0.147, p:0.03) in the early pregnancy of pregnant women repectively. Conclusions. The present study shows that serum irisin level increases throughout the gestational period from early to middle pregnancy in women with GDM, but there is no effect of irisin on the development of GDM.

Background. People chew betel nut (Areca catechu) for physical work and stress reduction, but it contains arecoline, which has both therapeutic value and untoward effects on endocrine and gonadal functions. Objective. Aim of the present study is to investigate its role on adrenal with its target in metabolic stress in mice. Materials and methods. Mice were deprived of water / food, each for 5 days / treated with arecoline (10 mg / kg body wt daily for 5 days) / arecoline after water or food deprivation, for 5 days each. Results. Water or food-deprivation caused adrenocortical hyperactivity, evident from abundance of enlarged mitochondria and smooth endoplasmic reticulum (SER) with elevation of corticosterone level (C: 68.31 ± 2.30, WD: 159.31 ± 4.10 / FD: 194.12 ± 3.40 μg/ mL). Arecoline treatment alone or in water deprivation (C: 68.31 ± 2.30, AR: 144.50 ± 4.33, AR+WD: 194.42 ± 3.35 μg/ mL) / food deprivation (AR + FD: 180.89 ± 4.51 μg/ mL) stress also stimulated adrenocortical activity as recorded in metabolic stress. In contrast, adrenomedullary activity was not altered following water/ food deprivation. Arecoline treatment alone or in metabolic stress suppressed adrenomedullary activity by showing depletion of chromaffin granules (E/NE?), epinephrine (E) and norepinephrine (NE) concentrations. Both the stress decreased blood glucose and liver glycogen levels. Arecoline treatment decreased blood glucose level, with a rise in liver glycogen level, but elevated blood glucose level in water deprivation unlike in starvation. Conclusion. Arecoline alone or in metabolic stress involves adrenal and probably other endocrine glands (pancreas, posterior pituitary and rennin-angiotensin system) to maintain homeostasis in metabolic stress in mice.