ACTA ENDOCRINOLOGICA (BUC)

An 18 years old, tall man presented for circumoral numbness, paresthesias, and hypocalcaemia, without carpopedal spasm or seizures. Previous medical history revealed bilateral cataract and osseous cysts on limbs at the age of 12. Hypocalcaemia resistant to calcium treatment and mild increased TSH levels were present. At diagnosis, we noticed a normal phenotype with tall stature, moderate hypocalcaemia (5.8 mg/dL), hyperphosphatemia (5.08 mg/dL) and significantly higher than normal intact parathormone (PTH) levels (518 pg/mL), in the presence of normal serum levels of 25-hydroxy vitamin D (53.56 ng/mL). The mother and the family members have been found in good health. All these data strongly suggested sporadic pseudohypoparathyroidism type Ib (PHP-Ib), but with some features of PHP - type Ia, like the osseous cysts. We were not able to perform molecular genetic tests. The nearly complete recovery of clinical and biochemical signs (normalization of PTH, calcaemia, phosphatemia, and a normal DXA osteodensitometry) after 2 years of chronic treatment with activated 1,25- dihydroxycholecalciferol (2.00-0.75 μg/day) indirectly, but strongly confirmed the diagnosis of pseudohypoparathyroidism. The patient may have resistance to TSH evidenced by high TSH\r\n(range 4.8-7.5 mIU/L), with normal thyroid hormone levels, absence of goiter and normal TPO antibodies. The TRH test (400 μg i.v.) showed a response of TSH, and also of serum thyroxine and triiodothyronine in a range that did not clarify the diagnosis. This association of the resistance to TSH with type Ib PHP was relatively recently reported by two groups (17,20) and before them it was reported only in PHP-Ia. Our patient also showed mild thrombocytopenia, with normal bleeding time, indicating also a possible Gsα deficiency in platelets. In conclusion, our patient with sporadic pseudohypoparathyroidism without clinical phenotype of Albright hereditary osteodystrophy is highly suggestive for the type Ib PHP. A possible resistance to TSH and thrombocytopenia associated are features related to the genetic mechanisms found also in type Ia PHP. It is tempting to suggest that this case is one of the new variants of pseudohypoparathyroidism-Ib, recently reported.

Aims. To assess the impact of prognostic factors on the outcome of ovarian carcinoma (OC) and to determine the difference between pre and postmenopausal patients. Design. Retrospective cohort, single centre study Subjects and Methods. One-hundred-sixty patients with stage IC-IV OC diagnosed between 2004-2016 were included. Treatment consisted in primary surgery followed by adjuvant chemotherapy (n=127, 79.4%), neoadjuvant chemotherapy followed by surgery (n=27, 16.9%) and chemotherapy alone (3.7%). Results. At diagnosis 62 patients (38.8%) were premenopausal. Most patients presented with advanced OC (stage III/IV, 63.1%). After a median follow-up of 60 months, median progression free survival (PFS) for all stages was 36 months and median overall survival (OS) was 96 months. Postmenopausal patients had a poorer oncologic outcome compared with pre-menopausal women (PFS 24 vs. 72 months, p=0.0001, HR=2.32). Other clinical prognostic factors identified were performance status 1 vs. 0 (p=0.0001), ascites (p=0.027). Pathology prognostic factors were tumour grade (G1 vs. G2 and G3, p=0.0001) and endometrioid subtype compared to serous (p=0.008). Patients with residual disease after surgery had an increased risk of recurrence and death (HR=6.1, p=0.0001 and HR=4.2, p=0.0001). Conclusion. Premenopausal patients had a better oncologic long-term outcome and stage, ascites, grading, residual disease, were independent prognostic factors.

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.

In this study we aimed to assess amiodarone&#8217;s effects on thyroid hormones, C reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor (TNF-&#945;) profile in amiodarone-induced thyrotoxicosis (AIT) and their relationship with arrhythmias. In 60 patients with AIT (29M/31F), aged 59.7 ? 1.5 years and 105 hyperthyroid patients (25M/80F), aged 59.4 ? 1 years, TSH, total T3, total T4, free T4 were measured by IRMA or microenzymatic immunoassay. In 11 AIT patients and 26 patients with common hyperthyroidism, without significant Graves&#8217; ophthalmopathy, CRP, IL-6 and TNF-&#945; were measured by chemiluminescent immunoassays. AIT patients showed significantly lower T3 levels (273.82 ? 18.76 ng/dL) as compared to common thyrotoxicosis (361.89 ? 13.47 ng/dL), p<0.001, while T4 and FT4 were similar. AIT patients showed similar CRP, IL-6 and TNF-&#945; levels to common hyperthyroidism (10.22 ? 3.03 mg/L vs. 6.31 ? 2.33 mg/L, p=0.11, for CRP, 17.46 ? 13.09 pg/mL vs. 6.46 ? 1.14 pg/mL, p=0.65, for IL-6, and 9.9 ? 1.76 pg/mL vs. 12.85 ? 2.22 pg/mL, p=0.22, for TNF-&#945;, respectively. Patients with arrhythmias (n=19) showed significantly higher CRP, IL-6 and TNF-&#945; levels as compared to patients without arrhythmias (n= 18): 10.81 ? 3.35 mg/L vs. 3.96 ? 1.08 mg/L, p=0.05, for CRP, 15.15 ? 7.52 pg/mL vs. 4.02 ? 0.74 pg/mL, p=0.007 for IL-6, and 15.16 ? 3.33 pg/mL vs. 9.2 ? 0.82 pg/mL, p=0.037 for TNF-&#945;. In conclusion, AIT showed a similar pattern of proinflammatory cytokines to common hyperthyroidism. Increased CRP, IL-6 and TNF-&#945; are found only in patients with thyrotoxicosis associated with atrial fibrillation or other arrhythmias.

Aim: We aimed to assess the final outcome of combined therapeutic approaches in patients with macroprolactinomas that were resistant to dopamine agonists (DA).\r\nPatients: Records of patients with macroprolactinoma hospitalized in the Institute of Endocrinology, Bucharest, between 1978-2005, were reviewed. There were 29 eligible patients resistant to DA therapy (8 men and 21 women), out of 119 patients with macroprolactinomas (24.4%); age at diagnosis of the resistant patients ranged between 16-59 years (31.9 ? 2.4 years), with mean prolactin (PRL) levels 2,110.2 ? 656.6 ng/mL (range 42-16,000 ng/mL). The mean maximal tumor diameter was 2.7 ? 0.2 cm (range 1-6.8 cm).\r\nMethods: Rapid fluoroimmunoassay using Europium was used for hormonal levels; computed tomography imaging and/or MRI were used to assess tumor size. Study design: The resistance to DA drugs was evaluated using initial criteria: the lack of prolactinoma response to current daily dose of Bromocriptine (BRC) 7.5 mg/day or to Cabergoline (CAB) up to 2 mg/week for at least 6 months (step 1) or final criteria: the lack of response to high BRC doses (30 mg/day) or CAB doses between 2.5-4 mg/week for at least 6 months (step 2). The lack of response was considered if PRL levels remained above the upper normal limit (20 ng/mL) and the tumor mass size decreased by less than 50%. All resistant cases at step 1 received thereafter maximal medical therapy with DA drugs, according to step 2. Thereafter, resistant macroprolactinomas after step 2 were submitted to step 3 - high voltage radiotherapy ? surgery. Serum PRL levels and tumor size were finally evaluated 110 ? 26.5 months later (range: 6-381).\r\nResults: Outcome of medical therapy with DA (n=29): Overall, 7 out of 29 resistant macroprolactinomas (24.1%) were successfully treated by increasing BRC dose (n=5) or changing BRC to CAB (n=2). But 22/119 (18.5%) patients remained resistant to DA drugs independent of dose, duration or type of drug used. 14 patients failed to normalize PRL levels despite CAB treatment in doses up to 7 mg/week. Outcome of radiotherapy alone or combined with surgery (n=15): PRL normalization was achieved in 4 patients out of the only 7 assessed at least at 18 months after radiotherapy. Withdrawal of DA therapy revealed 2 cured cases, both after radiotherapy and surgery. Outcome of surgery: Only one patient normalized PRL levels after surgery, but she soon relapsed. Apparently, only one case of acquired resistance to DA drugs was revealed. We found that 15.1% (18/119) of the patients with macroprolactinoma did not finally normalize their serum PRL even after combined therapy approaches (DA + radiotherapy ? surgery), after 79 ? 17.4 months (range 6 to 206 months) treatment total duration and 45.4 ? 19 months (range 3 to 206 months) after radical therapies, respectively.\r\nConclusion: In summary, the resistance was successfully treated in 38% cases (11 out of 29).

-

-