ACTA ENDOCRINOLOGICA (BUC)

Hyperosmolar hyperglycemic non-ketotic state is a life-threatening emergency manifested by a marked elevation of blood glucose, hyperosmolarity, and little or no ketosis. It most frequently develops in middle-aged or elderly patients, often in the setting of previously mild type 2 diabetes and in the presence of one of the established risk factors (e.g. infection, cerebrovascular accident, myocardial infarction). We present the case of a 48 years old woman with no past history of diabetes who developed hyperosmolar hyperglycemic nonketotic state after transsphenoidal surgery for a large macroprolactinoma. Despite having symptoms (secondary amenorrhoea and galactorrhoea) for many years the patient only had inconsistent medical follow-up and eventually she developed optic chiasm syndrome. She was referred for pituitary surgery performed by transsphenoidal route. After surgery there was marked improvement of the visual signs but few days after intervention the patient presented with polydipsia, polyuria and paresthesiae. Based on laboratory tests that showed a markedly elevated blood glucose level (1088 mg/dl), hyperosmolarity, no acidosis therefore, a diagnosis of hyperglycemic hyperosmolar state was made. With rehydration and insulinotherapy she recovered and the evolution was favourable over weeks with discontinuation of insulin administration. The patient still had high prolactin level after surgery (3060.3 ng/dl) so we also initiated dopamine agonist bromocriptine treatment. In addition to the well known effects of dopamine agonist upon prolactinoma it also has beneficial effects on glycemic control in diabetics (it reduces insulin resistance, both fasting and postprandial plasma glucose levels and HbA1c levels). We discuss the possible explanations of the syndrome and the effects of bromocriptine treatment.

INTRODUCTION: Sleep apnea syndrome is a common manifestation of acromegaly. Although the obstructive type of apnea was thought to be predominant there are some reports suggesting that central apneic episodes show a high rate and are related to abnormalities of central respiratory control.\r\nAIM: The present study determines the presence and severity of central sleep apnea syndrome in patients with acromegaly compared with obese subjects.\r\nMATERIALS AND METHODS: 35 consecutive acromegalic patients (min GH (growth hormone) during oral glucose tolerance test (OGTT) 6.6 ng/ml) and 19 obese subjects (BMI=44 kg/m2) were polisomnographically recorded between 10 p.m and 6 a.m. Sleep and respiratory disturbances were manually staged according to standard criteria.\r\nRESULTS: The prevalence of sleep apnea syndrome in acromegaly group was 45.7% (16 out of 35 patients). The median of minimum GH level during OGTT was 8.3 ng/ml in apnea group and 5.16 ng/ml in nonapneic group (p>0.05). In acromegaly group with severe sleep apnea syndrome central apnea rate was greater than 10% in 6 out of 7 subjects with REM sleep and in 7 out of 10 with NREM sleep whereas in obesity group this percent was present in 6 out of 18 (REM sleep), respectively 7 out of 19 (NREM sleep).\r\nCONCLUSIONS: The study confirms the high prevalence of sleep apnea in acromegaly. GH serum level is not an indicator for the presence and severity of sleep apnea. Although the total time of central apnea per hour of sleep did not differ between the two groups, the percent (rate) of central apnea was significantly greater in acromegaly group.

The thyroid gland is one of the most vascularized organs in the body. However, metastatic disease to the thyroid gland is rare. When it does occur kidney is the most common primary tumor site, followed by melanoma, lung, breast, esophagus, uterus and colon carcinoma. We describe the case of an isolated thyroid metastasis from clear cell renal carcinoma occurring 16 years after nephrectomy. An 82 years-old woman presented for the recent growth of a right thyroid nodule, diagnosed 3 years before, when a fine needle aspiration biopsy found a benign cytology suggesting a well-differentiated follicular thyroid adenoma. Her medical history included type 2 diabetes mellitus, atrial fibrillation and a right nephrectomy for a clear cell renal carcinoma done 16 years before. The patient has lost weight but she was otherwise asymptomatic. The right lobe goiter was painless, firm, and mobile with deglutition, without signs of local compression or latero-cervical lymphadenopathy. Thyroid ultrasonography revealed an enlarged (9.9 cm) macronodular right lobe, with multiple cystic areas, with normal left lobe and a thrombus in the right internal jugular vein. Thyroid function tests were normal. The patient was suspected of thyroid carcinoma and underwent a near total thyroidectomy. Histopathological examination revealed a metastasis of clear cell renal carcinoma in the right thyroid gland lobe (8.5/5/5 cm). Further imaging showed no primary tumor or other metastases. Metastatic renal carcinoma to the thyroid should be considered in any patient presenting with a thyroid mass and a medical history of operated renal cell carcinoma, since it can occur up to 25 years after nephrectomy.

Introduction. Surgery for thyroid cancer carries a higher risk of morbidity given the region’s complicated anatomy, the setting of malignancy and extent of the surgery. Aim. To investigate the rate of complications related to the recurrent nerve and parathyroid glands lesions in patients with thyroid carcinoma that undergo thyroid surgery and lymph node dissection. Patients and Methods. The data of 71 patients who underwent total thyroidectomy and 19 patients who underwent total thyroidectomy and central neck dissection with various associated neck dissection techniques were investigated using appropriate statistical tests. Results. As expected, the rate of recurrent nerve injury observed in the neck dissection group was higher than in the total thyroidectomy group (15.7% vs. 2.8%, p=0.05). As for postoperative hypocalcemia, the rate observed in the neck dissection group, both for postoperative day 1 (p<0.0001) and day 30 (p=0.0003) was higher than in the total thyroidectomy group (68.4% vs. 19.7% postoperative day 1, 31.5% vs. 4.2% postoperative day 30). Conclusions. The risk of morbidity concerning the recurrent nerve injury and postoperative hypoparathyroidism increases with the extent of surgery. Extensive surgery may achieve proper oncologic outcomes but increases the risk of postoperative morbidity and decreases quality of life. In deciding for extensive surgery, both patient and medical team need to understand these risks.

Objective. To monitor the iodine status in Romanian schoolchildren and neonates after 20 years of mandatory salt iodization. Subjects and methods. In a national representative sample of 1352 children (7-12 years) we measured median urinary iodine concentration (mUIC) and creatinine (UCC) in spot urine samples and investigated household use of iodized salt. From 18349 neonates registered in the MEDILOG program for TSH screening we calculated the percentage of neonatal TSH >5 mIU/L (<3% indicating adequate iodine intake). Results. mUIC in schoolchildren was 141 μg/L (bootstrapped 95% CI 134, 146), showing adequate iodine intake in all but 1 county; mUIC was similar in historical endemic and non-endemic counties (140 μg/L and 143 ug/L, respectively) and in urban and rural areas (140 μg/L and 142 μg/L, respectively); mUIC/UCC = 118 ug/g. Iodized salt was used in 62% of households. In children using iodized salt (61.7%), mUIC was higher than in those using coarse (non-iodized) salt (24.6%): 150 vs. 121 μg/L (p<0.001). The percentage of nTSH >5 mIU/L was 14.7% (3.2%-27.3%), higher in non-endemic counties and urban areas. Conclusion. The current salt iodization program for households and bakery industry ensures an adequate iodine intake in schoolchildren. Discordantly, nTSH levels indicate a mild-moderate ID in neonates, suggesting ID in pregnant women. The percentage of households using iodized salt is below the recommended >90% needed for an efficient ID prevention program. More efforts should be directed to increase the public awareness on the health risks of ID and the benefits of ID prevention, notably for the neurointellectual development in children.

Endocrine disruptors (EDs) are considered to have an impact on the function of reproductive axis at different levels as well on reproductive organs in both sexes. Complexity of female reproductive system influenced with various stressors including EDs lead to morphological and functional alterations. This is resulting in modulation of neuroendocrine regulation with consequent developmental irregularities and derangements, causative infertility, endometriosis as well as premature ovarian insufficiency or polycystic ovary syndrome. A number of experimental clues was obtained on female animal models using various EDs such as synthetic estrogens and phytoestrogens, neurotransmitters, pesticides or various chemicals. These substances lead towards consequent derangement of the neuroendocrine control of reproduction from early phases of reproductive development towards different phases of adult reproductive period. This text will address some novel insights into the effects of EDs on neuroendocrine regulation of gonadal axis, effects on ovaries as well on endometrium during implantation period.

Meningiomas are the most common benign tumors of the brain, accounting for about 15 to 20% of all primary brain tumors. They are more common in females than in males and are most likely found in the sixth and seventh decades. Meningiomas arise from leptomeninges. Even the hyperostosis of the overlying skull occurs in 15-20% of cases and most of them have the tendency to calcify. The biological one can find hypercalcemia in a patient with cerebral meningioma, only if it associates other diseases like hyperparathyroidism. Between January 2000 and December 2006, in the Department of Pituitary and Neuroendocrine Pathology of the &#8220;C.I.Parhon&#8221; Institute of Endocrinology, Bucharest there have been admitted 29 patients with primary hyperparathyroidism, 7 males and 22 females. From the 22 women with primary hyperparathyroidism, 3 cases presented multiple endocrine neoplasia type I and 19 sporadic primary hyperparathyroidism. In the same period of time we found in 3 of these cases the association between sporadic primary hyperparathyroidism and cerebral meningiomas. We present the cases of three female patients of 56, 55, respectively 58 years old, diagnosed with primary hyperparathyroidism during the follow-up for nontoxic goiter. Two of them were known with cerebral meningiomas, unsuccessfully surgically approached, while the third one was newly diagnosed with meningioma, based on neuroimaging. There are a couple of studies regarding the association between cerebral meningiomas and the multiple endocrine neoplasia type 1 (MEN 1), but we found in the literature only three cases of both cerebral meningioma and sporadic primary hyperparathyroidism. Clinicians should be aware of the possible association between cerebral meningiomas and primary hyperparathyroidism.

The objective of this review is to summarise what is known about mortality in ACTH dependent Cushing&#8217;s disease (CD). Specifically, mortality in other causes of Cushing&#8217;s\r\nsyndrome (CS) such as ectopic ACTH syndrome and adrenal adenomas is not considered because of the relative rarity of these causes of CS. Six papers addressed mortality of CD in relation to the background population.\r\nThe overall mortality in CD is increased 2-4 fold, but in patients that achieved early remission of hypercortisolaemia the standardised mortality ratio (SMR) is not different from that of the background population. Those in whom hypercortisolaemia was not controlled had a poor outcome (SMR 4-11), and died prematurely. Persistence of disease, older age at\r\ndiagnosis, and presence of hypertension appear as the main determinants of mortality. However, there are several caveats to these conclusions: 1. The number of patients studied is small and the number of deaths even smaller; 2. On average the patients were young (40yrs old) at diagnosis, their follow-up was 10 yrs, and by the age of 60 the expected number of deaths in the background population is going to be small so that differences in causes of death will be difficult to ascertain; 3. SMR of 1.5 -2.0 for patients in remission may not be statistically significant in the reported studies but could become so with larger numbers followed for a much longer time (30-40 yrs). Notwithstanding these caveats, it is encumbent on us as endocrinologists not only to treat the symptoms and complications of CD but also to ensure that patients are &#8216;cured&#8217; of their hypercortisolism in order to maximise long-term survival.

A brief synopsis on the past three and a half decades of intracellular insulin research is given as it relates primarily to the human system. Thereby, a particular emphasis is placed on insulin binding and inactivation of the central tumor suppressor retinoblastoma protein (RB) and, moreover, on insulin degradation by the putative antioncoprotein insulin-degrading enzyme (IDE). Finally, the potential for (anticancer) therapeutics that target intracellular insulin is outlined.

Context. The effects of COVID-19 on the adrenocortical system and its hormones are not well known. Objectives. We studied serum cortisol, serum adrenocorticotropic hormone (ACTH), and their ratio in hospitalized non-critically ill COVID-19 patients. Design. A prospective case-control study. Methods. The study participants were divided into 2 groups. Group 1 consisted of 74 COVID-19 patients. The second group consisted of 33 healthy persons. Early admission above hormones levels was determined and compared between the study groups. Besides that, COVID-19 patients were grouped according to their Glasgow Coma Score (GCS), CURB-65 score, and intensive care unit (ICU) requirement, and further sub-analyses were performed. Results. There were no significant differences in the mean age or gender distribution in both groups. In the patients’ group, the serum ACTH concentration was lower than in the healthy group (p<0.05). On the other hand, the serum cortisol levels and cortisol/ACTH ratio of the patients’ group were significantly higher than of the healthy controls (p<0.05, all). Further analyses showed that, although serum cortisol and ACTH levels were not high, the cortisol/ACTH ratio was higher in COVID-19 patients with low GCS (<15) than patients with normal GCS (=15) (p<0.05). In COVID-19 in patients with different CURB-65 scores, the cortisol/ACTH ratio was significantly different (p<0.05), while serum cortisol and ACTH were not different in groups (p>0.05). Serum cortisol levels and cortisol/ACTH ratio were higher but ACTH level was lower in the ICU needed COVID-19 patients than in patients who do not need ICU (p<0.05). Conclusion. Our pilot study results showed that the cortisol/ACTH ratio would be more useful than serum cortisol and/or ACTH levels alone in evaluating the adrenocortical system of COVID-19 patients. Still, further detailed studies are needed to confirm these.