ACTA ENDOCRINOLOGICA (BUC)

Published data sustain the involvement of diet on pathogenesis of immune-mediated diseases.\r\nAim. To determine if the high fat diet (HFD), in the absence of obesity, could modulate the altered pulmonary arteries\r\nreactivity associated to allergic lung diseases.\r\nMaterials and Methods. Obese resistant rats were divided into 2 groups: standard chow diet and HFD. Randomly chosen rats from both groups were sensitized against ovalbumin. The histological aspect and reactivity of pulmonary arteries were comparatively assessed. Taking into account the involvement of adipokines on obesity associated vascular reactivity alteration we also studied the vasomotor effects of few adipokines on pulmonary vessels.\r\nResults. Lung histological examination revealed that HFD aggravated the remodelling of pulmonary arteries and\r\ninflammation of lung parenchyma. The HFD amplified the phenylephrine - induced contractions. Angiotensinogen amplified and apelin inhibited the Phe contractile effects on sensitized HFD fed rats.\r\nConclusion.These effects could be at least mediated, by both the alteration of adipokines vasomotor effects and\r\ninflammation associated to pulmonary allergic disease.

Prader Willi syndrome is a complex disease caused by the lack of expression of paternally inherited imprinted genes on chromosome 15q11.2-q13. Typical clinical features are hypotonia and feeding difficulties in infancy, followed by hyperphagia and progressive obesity, distinctive dysmorphic features, intellectual disability and behavioural problems. In this paper we present clinical, metabolic and endocrine aspects in five genetically confirmed patients with PWS. Data about thyroid dysfunction, GH deficiency, adrenal insufficiency, and LH/FSH disorder caused by hypothalamic dysfunction in PWS were collected and analyzed. Cardiovascular metabolic profile was also assessed, based on plasma lipids, blood glucose, HbA1c values, and measurements of body weight and blood pressure. Clinical features present in all our patients were marked hypotonia and feeding difficulties in infancy, obesity, dysmorphic face, viscous saliva, small hands and feet, intellectual disability and characteristic behaviour. Adrenal function appeared to be normal in all patients; mild hypothyroidism was identified in one patient; sex development abnormalities were present in three patients and GH levels were within lower normal range in all patients. GH therapy was initiated in two patients, both with unevolutive skeletal anomalies, with good results and no side-effects. Only one patient had a normal lipid profile, underlying the importance of early detection and treatment of cardiovascular risk factors. Our study also illustrates the challenges raised by some features very rarely described in PWS (Blount disease and multiple allergies).

Thyroid carcinoma is rare in children and adolescents and has a relatively favorable prognosis. As in adults, the incidence in girls is double than in boys. It has a little risk of mortality, but a high risk of recurrence. Patients younger than 15 years old at diagnosis are considered more likely to have more extensive tumor at diagnosis than patients who are 15 years and older. We report two patients: an 11 years old girl with Fallot tetrallogy and papillary thyroid cancer and a 13 years old girl with Graves’ disease treated with antithyroid drugs for three years and thyroidectomized at 17 years old with an incidental thyroid microcarcinoma. Those unusual associations are discussed regarding therapy and follow-up issues.

Objective. Romania has no national guidelines for hypothyroidism treatment, nor are there any recommendations from national societies to adhere to international guidelines. Our aim was to identify the attitudes of Romanian physicians relating to hypothyroidism treatment focusing on available formulations of levothyroxine (LT4). Methods. All 748 members of the Romanian Society of Endocrinology were invited to participate in a web-based survey. A total of 316 (42.24%) members responded, of whom 222 (70.2%) completed all questions. Results. Half of the respondents recommended LT4 treatment in euthyroid patients, from 3.6% in euthyroid patients with obesity to 36.4% in euthyroid females with infertility associated with high levels of thyroid antibodies. LT4 was considered the preferred treatment for hypothyroidism (compared to combination treatment of LT4 with LT3 or LT3 alone) by 98.6% of respondents. LT4 in liquid solution was preferred over tablets if malabsorption is suspected (56.5% vs. 27.3%), for patients with unexplained poor biochemical control (52.5% vs. 22.9%) and for patients not able to adhere to ingesting LT4 fasted (74.0% vs. 9.8%). The most and least probable explanations for persistent symptoms in patients with hypothyroidism who achieve a normal TSH under medication were “psychosocial factors” and “burden of having to take medication”, respectively. Conclusion. A significant proportion of Romanian physicians would use LT4 in some groups of euthyroid patients, contrary to current evidence. The preferred treatment for hypothyroidism was LT4. Alternative LT4 formulations (liquid solution) are considered in specific clinical conditions. Diversification of available thyroid hormone formulations was readily incorporated into everyday practice.

Glucose intolerance (impaired fasting glucose [IFG], impaired glucose tolerance [IGT] or diabetes mellitus) due to insulin resistance is a frequent complication of acromegaly due to excessive growth hormone (GH) production. Long-acting somatostatin analogs are known to reduce the GH and IGF-1 serum levels, and to inhibit at the same time the pancreas insulin release. The effect upon acromegalic patients who express IFG before therapy is controversial. We here present two male patients, 66 and 36 years old, with active acromegaly and IFG who were submitted to a treatment with long-acting somatostatin analog lanreotide. After being diagnosed with active acromegaly with high nadir serum GH levels along oral glucose tolerance test (OGTT), i.e. 149 ng/mL and 43 ng/mL respectively, the patients underwent complex therapy (surgery and radiotherapy) which reduced the GH serum levels (20.7 ng/mL and 3.5 ng/mL respectively) without curing the disease. The patients developed IFG with fasting serum glucose levels of 113 mg/dL and 101 mg/dL, respectively. The treatment with the long-acting somatostatin analog lanreotide (30 mg i.m., every two weeks) decreased the GH serum levels close to normal limits (1.5 ng/mL and 1.6, ng/mL respectively). The treatment with lanreotide normalised the fasting serum glucose levels (91 mg/dL and 81 mg/dL, respectively) together with a reduction of serum insulin levels from 14.2 mU/mL to 8.7 mU/mL and from 25.4 mU/mL to 11.5 mU/mL, respectively (HOMA decreased form 3.96 to 1.97 and 6.33 to 2.3, respectively). We discuss the mechanisms by which lanreotide can improve glucose tolerance in patients with active acromegaly despite lowering the serum insulin levels through a direct effect on insulin secretion.

Introduction. Acromegaly is a chronic disease associated with high mortality rate if untreated. The aim of the study is to evaluate mortality ratio in Romanian patients with acromegaly in latest years, with new therapeutic options. Patients and Methods. This retrospective study analyzed 336 (111M/225F, mean age 48.13±12.40 years) consecutive patients with acromegaly between 1st January 2001 and 31 December 2014, median follow-up 7.36 years (0.48-13.99 years). PAMCOMP computation program assessed standardized mortality ratio (SMR). Kaplan Meier curve was used for comparison between of different cut-off levels of the last GH level on survival. Serum GH levels were measured by IRMA (sensitivity 0.1 ng/mL). Results. During follow-up 2596.34 person-years, 41 patients died, with a SMR of 1.34 (CI 0.96-1.82). Mean age at death was 63.19±11.66 years. Females with acromegaly died 83% more frequently than women in general population: SMR-1.83 (CI 1.21-2.67). Females were older at diagnosis (p=0.006), and were less probable to receive substitution of gonadotrophic failure than males (p<0.001). Independent factors correlated with mortality were age at baseline (p<0.001, HR=1.07), last GH level (p=0.003, HR=1.01) and systolic blood pressure (p=0.029, HR=1.02). Patients with last GH level ≤ 1 ng/mL had a better survival than patients with GH>1 ng/mL (p Log Rank=0.002). SMR of patients with last GH >1 ng/mL was 1.59 (CI 1.08-2.26) for the entire group, 2.2 (CI 1.32-3.44) for females and 1.3 (CI 0.67-2.29) for males. Conclusion. Patients with acromegaly have a high mortality ratio compared to general population, especially in women and those with post-therapeutic serum GH levels over 1 ng/mL. Longer follow-up is needed for the evaluation of the effect of new therapies on mortality.

Background. Patients with acromegaly (caused by growth-hormone-secreting pituitary adenomas) are at increased risk of hypopituitarism, in particular hypogonadotropic hypogonadism, before and after multimodal therapy. In affected women of reproductive age, fertility is impaired and complex fertility treatments are needed to achieve conception. C ase presentation. We present the case of a young woman with acromegaly caused by a GH-secreting macroadenoma with suprasellar and bilateral cavernous sinus extension; hypogonadotropic hypogonadism and secondary hypothyroidism were present from the initial evaluation. Neurosurgical intervention was repeatedly recommended but the patient refused it initially; also she was non-compliant to the medical treatment of acromegaly. Transsphenoidal tumor debulking with adjuvant gamma-knife radiotherapy was eventually performed. Following treatment persistent active acromegaly and hypogonadotropic hypogonadism were diagnosed. Under chronic estroprogestative replacement therapy, the patient conceived and delivered a full-term healthy newborn without any complications. Possible mechanisms are discussed. Conclusions. Secondary hypogonadotropic hypogonadism in pituitary patients, even when considered permanent (after surgery and radiotherapy), can exceptionally allow spontaneous conception and normal course of pregnancy.

Graves&#8217; 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&#8217; disease and infiltrative ophthalmopathy class IV according to Werner classification, non-responsive to Methylprednisolone antiinflammatory therapy and to irradiation. From anamnesis we mention Graves&#8217; disease&#8217;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.

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