ACTA ENDOCRINOLOGICA (BUC)

OBJECTIVES: This study was carried out on 1290 patients, whose choroids plexus and pineal gland were examined on computed tomography. Aim: To check the correspondence between the choroid plexuses and the pineal gland calcifications along age groups and sex; and the connections between these calcifications and associated pathology.\r\nMATERIALS AND METHODS: The study group consisted of patients of both sexes, within six age intervals.\r\nRESULTS: In order to classify the calcification variants, eight types of combinations were ordered and can be seen in CT: two refer to extreme variants: totally uncalcified (type 1) and totally calcified (type 8); bilateral, symmetrical variants (types 4 and 5); the other four types include the asymmetrical calcifications (2, 3, 6 and 7). After the anthropological study the results demonstrate that there are significant differences between calcification of the choroids plexus and those of the pineal gland with the two sexes, on age groups and pathological ground. For type 1-totally uncalcified the maximum frequency is around 70% with ages under 19. For type 8 - totally calcified, bilateral, the maximum frequency is around 50% with age groups 48-59 and 60-71. For type 4 - calcification only of choroid plexus, one finds a continuous increase from about 10% at the first age group to about 25% at the last group, while for type 5- calcification only of the pineal gland the frequency is 10%−20%. We started from the hypothesis that the presence of these calcifications is physiological, and has an active adaptative metabolic part depending on many factors, among which the individual constitutional ground is also present.\r\nCONCLUSIONS: The age is not the main cause of the calcification types, but a process of adaptative-reactive variability of interface type, playing an integrating mediating part.

Background: Germline aryl hydrocarbon receptor-interacting protein (AIP) mutations are found in familial isolated pituitary adenoma syndrome (FIPA) families and in a small number of sporadic pituitary adenoma (PA) patients. Although the tumorigenic mechanisms of AIP mutations are unclear, truncating mutations are considered pathogenic, but missense mutations are difficult to evaluate. p.R16H (c.47G>A) is a controversial AIP variant of unknown significance. Aim: To describe a new PA case associated with AIP p.R16H. Patients and methods: One AIP p.R16H non-functioning pituitary adenoma (NFPA) case identified by mutation sequencing screening of sporadic PA patients; 108 controls were screened for p.R16H. Results: The 38 yrs. old male NFPA patient had no family history of PA and harboured a heterozygous p.R16H variant. The proband and two brothers presented severe intellectual disability. Severe visual impairment was the initial symptom and clinical, biochemical and imaging examination demonstrated a large NFPA invading the right cavernous sinus. After transsphenoidal debulking, the remaining tumor continued growth. One of proband’s sisters was negative for p.R16H. Among controls, we identified one heterozygous p.R16H carrier, presenting a thyroid follicular neoplasm. Loss of heterozygosity analysis of the pituitary and thyroid tumors was not performed. Conclusions: We report two new occurrences of AIP p.R16H, associated with a NFPA and with a thyroid tumor. The NFPA patient was young and presented an invasive macroadenoma, features typical of AIP-mutated patients. Because the association between p.R16H and PAs has not been conclusively established, further research of p.R16H is warranted, in view of its implications for AIP genetic testing.

Aims. Earlier studies suggested that patients with nonfunctioning pituitary adenoma (NFPA) experience premature mortality, mostly from vascular diseases. The present study aims to identify risk factors associated with mortality in patients with NFPA. Methods. All consecutive patients admitted to a tertiary neuroendocrinology center for pituitary adenoma during 2001-2010 were screened. Only those with a final diagnostic of NFPA were retained. All 196 NFPA subjects (57.7% males, mean age 52.7±0.9 years) were followed-up for allcause mortality until December 31, 2011 (1298 person-years of follow-up). PAMCOMP software was used to calculate standardized mortality ratio (SMR), using the corresponding general population as reference. Cox regression analysis evaluated the independent hazards for mortality. Results. There were 26 deaths among 196 patients as compared to 20 expected. Standard Mortality Ratio (SMR) was 1.2 (95% Confidence interval (CI) 0.83-1.86). Females had a doubled mortality ratio: SMR 2.03 (95%CI 1.01-3.64), but males had a mortality ratio similar with general population: SMR 0.87 (95%CI 0.48-1.44). More patients with hypopituitarism for at least one axis deceased (22/156, 14.10%), as compared with patients without pituitary failure (1/22 patient deceased –2.07%), p=0.03. Prednison replacement for corticotrophin insufficiency (HR 1.46 (95%CI 1.12-1.90)) was correlated to mortality in females, but not in males, and mortality rose progressively with prednison dose (log rank: p=0.01). In males, last known maximal pituitary tumour diameter (HR 1.04 (95%CI 1.001-1.08) and age at baseline (HR 1.1 (95%CI 1.05-1.1) were modestly related to mortality. Conclusions. Females with nonfunctioning pituitary adenomas and hypopituitarism had a reduced life expectancy as compared with general population, possibly related to glucocorticoid substitution or a more severe pituitary insufficiency.

Background. Advances in imaging techniques have led to increasing discovery of\r\nadrenal and pituitary &#8220;incidentalomas&#8221;, tumors with normal endocrine function and no\r\ncompression mass effects. We evaluated the age at diagnosis (AD) in patients with benign\r\nnon-functioning adrenal incidentalomas, as compared to pituitary non-functioning tumors,\r\nin a series of patients from a national center of endocrinology. Methods. From 2,123\r\nconsecutive patients with adrenal and pituitary tumors hospitalized between 1977 - 2009,\r\n2,069 patients were analysed. The study groups included: group A - 137 patients with\r\nadrenal incidentalomas (AI), group B - 534 patients with pituitary incidentalomas (PI).\r\nControl groups included 1,398 patients: group C1 147 patients with adrenal carcinomas or\r\nbenign hormone-secreting adrenal tumors, and group C2, 1,251 patients with pituitary\r\nsecreting adenomas or large non-functioning pituitary macroadenomas (NFA). Imaging was\r\ndone by computed tomography and/or magnetic resonance after 1981 and by skull X-ray or\r\npneumoencephalography before 1981. Results. Mean age AD is more advanced in patients\r\nwith AI (53 ? 11.9 years, range 21 - 78 yr) than in patients with PI (36.8 ? 13.1 years, range\r\n10 - 81 yr), p < 0.01. AD was higher in AI than in patients with secreting adrenal tumors,\r\nbut similar in patients with adrenal malignancy. There is an age-related increase in the\r\nproportion of AI among patients with adrenal tumors, and of NFA, but not of PI, among\r\npatients with pituitary tumors. In patients aged over 65 years, 74% of patients with adrenal\r\ntumors have AI, while only 18% of patients with pituitary tumors have PI and 42% have\r\nNFA. AD in NFA (49.3 ? 13.1 yr, range 12 - 79 yr) was more advanced than in PI (p < 0.01).\r\nAD does not correlate with tumor size. Tumor growth occurred in 24% of AI (follow-up 3.0\r\n? 2.8 yr) and only in 0.7% of PI, p<0.01 (follow-up 3.1 ? 2.5 yr).\r\nConclusions. Adrenal non-functioning benign tumors show a clear association with ageing,\r\nin contrast with pituitary incidentalomas. It seems unlikely that most pituitary incidentalomas in\r\nyoung patients become large NFA, whose development seems to be also age-related. It is tempting\r\nto suggest that pituitary tumorigenesis starts earlier than adrenal tumorigenesis.

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.