The International Journal of Romanian Society of Endocrinology / Registered in 1938

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  • Endocrine Care

    Coculescu M, Anghel R, Badiu C, Caragheorgheopol A, Hortopan D, Dumitrascu A, Virtej I, Trifanescu R, Capatana C, Voicu D

    Additional effects of radiotherapy to dopamine agonists in the treatment of macroprolactinomas

    Acta Endo (Buc) 2005 1(1): 43-59 doi: 10.4183/aeb.2005.43

    Abstract References
    INTRODUCTION: The aim of our study was to evaluate the cure rate of macroprolactinomas treated for a long term (> 4 years) or a short term (<4 years) with dopamine agonists (DA) alone or combined with radiotherapy (RT). Sometimes pituitary\r\nsurgery was performed.\r\nMATERIAL AND METHODS: We performed a retrospective study in 111 patients with macroprolactinomas, hospitalized in the Institute of Endocrinology, Bucharest, between 1978-2005. There were two groups, according to the length of DA therapy: group\r\nA =41 patients, treated more than 4 years and group B =70 patients, treated less than 4 years. Overall, 25 patients underwent additional radiotherapy, 13 in group A and 12 in group B. 28 patients were submitted to pituitary surgery, 9 in group A and 19 in group B.\r\nRESULTS: The cure rate (i.e. normalization of prolactin=PRL level and absence or minimal residual tumor mass, stable minimum 2 years after DA withdrawal) was 5/41 (12.1%) in group A and none in group B. 48 out of 111 patients achieved significant improvement (serum prolactin level less than 20 ng/ml and tumor shrinkage more than 50%) during DA therapy, but not after DA withdrawal: 17/41patients (41.5%) in group A and in 31/70 patients (44.3%) in group B, p=NS. Radiotherapy produced an additional improvement: in serum PRL levels only in group A, in 4/13 patients- 2/8 patients responsive to DA therapy and 2/5 patients resistant to DA therapy. In group B, the 3 patients resistant to DA submitted to radiotherapy were evaluated before the interval necessary for maximal effect of radiotherapy, but in 4/9 patients responsive to DA, we noticed further reduction in tumor volume, 2/4 progressing from mild to significant tumor shrinkage and ? progressing from no shrinkage to mild shrinkage. After radiotherapy, the medium prolactin level was 5.1 ng/ml in 10 patients from both groups on low bromocriptine (BRC) dose (7.5 mg/day), significantly less than in patients without radiotherapy, i.e. than in 19 patients from group A (serum PRL 49.5 ng/ml, p=0.02) and in 29 patients from group B (serum PRL 30.3 ng/ml, p=0.01). So, the daily BRC dose could safely decrease from 30 mg/day to 7.5 mg/day in those patients previously submitted to radiotherapy. Among 23 patients resistant to initial DA treatment, only 8 patients were submitted to radiotherapy, 2 became responsive to DA thereafter and 2 others obtained a significant decrease of prolactin levels.\r\nCONCLUSIONS: The overall cure rate is quite low in prolactinomas and it was noticed only after long-term treatment with dopamine agonists; it was improved up to 12.1% by the additional high voltage radiotherapy, useful even in DA resistant cases. The addition of radiotherapy is indicated for the cure of most prolactinomas.
    1. Coculescu M, Simionescu N, Oprescu M, Alessandrescu D. Bromocriptine treatment of pituitary adenomas. Evaluation of withdrawal effect. Revue Roumaine Med Endocrinol 1982; 21:157-168.
    2. Molitch M. Prolactinoma. In: Melmed S, editor. The pituitary. Toronto, New York: Blackwell Publishing, 2002: 455-495.
    3. Thorner MO, Perryman RL, Rogol AD, Conway BP, MacLeod RM, Login IS et al. Rapid changes of prolactinoma volume after withdrawal and reinstitution of bromocriptine. J Clin Endocrinol Metab 1981; 53(3):480-483. [CrossRef]
    4. Colao A, di Sarno A, Landi ML, Cirillo S, Sarnacchiaro F, Facciolli G et al. Long-term and lowdose treatment with cabergoline induces macroprolactinoma shrinkage. J Clin Endocrinol Metab 1997; 82(11):3574-3579. [CrossRef]
    5. Coculescu M, Hudita D, Gussi I, Gheorghiu M, Hortopan D, Caragheorgheopol A. Tumor size changes in prolactinomas treated with minimum bromocriptine throughout gestation. Gynecological Endocrinology 2000; 14(suppl 2).
    6. Badiu C, Ham J, Carnu R, Coculescu M. TRH synthesis in ?mute? thyrotropinomas: cause-effect or coincidence? J Cell Mol Med 2001; 5(1):88-91. [CrossRef]
    7. Coculescu M. Neuroendocrinologie clinica. Bucuresti: Editura Stiintifica si Enciclopedica, 1986.
    8. Colao A, di Sarno A, Cappabianca P, di Somma C, Pivonello R, Lombardi G. Withdrawal of longterm cabergoline therapy for tumoral and nontumoral hyperprolactinemia. N Engl J Med 2003; 349(21):2023-2033. [CrossRef]
    9. Molitch ME. Dopamine resistance of prolactinomas. Pituitary 2003; 6(1):19-27. [CrossRef]
    10. Molitch ME. Medical management of prolactin-secreting pituitary adenomas. Pituitary 2002; 5(2):55-65. [CrossRef]
    11. di Sarno A, Landi ML, Cappabianca P, Di Salle F, Rossi FW, Pivonello R et al. Resistance to cabergoline as compared with bromocriptine in hyperprolactinemia: prevalence, clinical definition, and therapeutic strategy. J Clin Endocrinol Metab 2001; 86(11) [CrossRef]
    12. Losa M, Mortini P, Barzaghi R, Gioia L, Giovanelli M. Surgical treatment of prolactin-secreting pituitary adenomas: early results and long-term outcome. J Clin Endocrinol Metab 2002; 87(7):3180- 3186. [CrossRef]
    13. Acquati S, Pizzocaro A, Tomei G, Giovanelli M, Libe R, Faglia G et al. A comparative evaluation of effectiveness of medical and surgical therapy in patients with macroprolactinoma. J Neurosurg Sci 2001; 45(2):65-69.
    14. Bevan JS, Webster J, Burke CW, Scanlon MF. Dopamine agonists and pituitary tumor shrinkage. Endocr Rev 1992; 13(2):220-240.
    15. Passos VQ, Souza JJ, Musolino NR, Bronstein MD. Long-term follow-up of prolactinomas: normoprolactinemia after bromocriptine withdrawal. J Clin Endocrinol Metab 2002; 87(8):3578-3582. [CrossRef]
    16. Sobrinho LG, Nunes MC, Santos MA, Mauricio JC. Radiological evidence for regression of prolactinoma after treatment with bromocriptine. Lancet 1978; 2(8083):257-258. [CrossRef]
    17. McGregor AM, Scanlon MF, Hall K, Cook DB, Hall R. Reduction in size of a pituitary tumor by bromocriptine therapy. N Engl J Med 1979; 300(6):291-293. [CrossRef]
    18. Orrego JJ, Chandler WF, Barkan AL. Rapid re-expansion of a macroprolactinoma after early discontinuation of bromocriptine. Pituitary 2000; 3(3):189-192. [CrossRef]
    19. Gen M, Uozumi T, Ohta M, Ito A, Kajiwara H, Mori S. Necrotic changes in prolactinomas after long term administration of bromocriptine. J Clin Endocrinol Metab 1984; 59(3):463-470. [CrossRef]
    20. Colao A, di Sarno A, Landi ML, Scavuzzo F, Cappabianca P, Pivonello R et al. Macroprolactinoma shrinkage during cabergoline treatment is greater in naive patients than in patients pretreated with other dopamine agonists: a prospective study in 110 patie [CrossRef]
    21. Delgrange E, Maiter D, Donckier J. Effects of the dopamine agonist cabergoline in patients with prolactinoma intolerant or resistant to bromocriptine. Eur J Endocrinol 1996; 134(4):454-456. [CrossRef]
    22. Webster J, Piscitelli G, Polli A, Ferrari CI, Ismail I, Scanlon MF. A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. Cabergoline Comparative Study Group. N Engl J Med 1994; 331(14):904-909. [CrossRef]
    23. Colao A, di Sarno A, Sarnacchiaro F, Ferone D, Di Renzo G, Merola B et al. Prolactinomas resistant to standard dopamine agonists respond to chronic cabergoline treatment. J Clin Endocrinol Metab 1997; 82(3):876-883. [CrossRef]
    24. Saveanu A, Morange-Ramos I, Gunz G, Dufour H, Enjalbert A, Jaquet P. A luteinizing hormonealpha- subunit- and prolactin-secreting pituitary adenoma responsive to somatostatin analogs: in vivo and in vitro studies. Eur J Endocrinol 2001; 145(1):35-41. [CrossRef]
    25. Ma W, Ikeda H, Yoshimoto T. Clinicopathologic study of 123 cases of prolactin-secreting pituitary adenomas with special reference to multihormone production and clonality of the adenomas. Cancer 2002; 95(2):258-266. [CrossRef]
    26. Senovilla L, Nunez L, de Campos JM, de Luis DA, Romero E, Sanchez A et al. Multifunctional cells in human pituitary adenomas: implications for paradoxical secretion and tumorigenesis. J Clin Endocrinol Metab 2004; 89(9):4545-4552. [CrossRef]
    27. Mignot M, Skinner DC. Colocalization of GH, TSH and prolactin, but not ACTH, with betaLHimmunoreactivity: evidence for pluripotential cells in the ovine pituitary. Cell Tissue Res 2005; 319(3):413-421. [CrossRef]
    28. Pellegrini I, Rasolonjanahary R, Gunz G, Bertrand P, Delivet S, Jedynak CP et al. Resistance to bromocriptine in prolactinomas. J Clin Endocrinol Metab 1989; 69(3):500-509. [CrossRef]
    29. Trouillas J, Chevallier P, Remy C, Rajas F, Cohen R, Calle A et al. Differential actions of the dopamine agonist bromocriptine on growth of SMtTW tumors exhibiting a prolactin and/or a somatotroph cell phenotype: relation to dopamine D2 receptor expressi [CrossRef]
    30. Jaquet P, Ouafik L, Saveanu A, Gunz G, Fina F, Dufour H et al. Quantitative and functional expression of somatostatin receptor subtypes in human prolactinomas. J Clin Endocrinol Metab 1999; 84(9):3268-3276. [CrossRef]
    31. Caccavelli L, Morange-Ramos I, Kordon C, Jaquet P, Enjalbert A. Alteration of G alpha subunits mRNA levels in bromocriptine resistant prolactinomas. J Neuroendocrinol 1996; 8(10):737-746. [CrossRef]
    32. Trifanescu R, Karavitaki N, Coculescu M, Turner HE, Wass JAH. What is the final outcome in patients with macroprolactinoma resistant to dopamine agonists? 24th Joint Meeting of the British Endocrine Societies, 4-6 April 2005, Harrogate, U.K, Endocrine A
  • Endocrine Care

    Oros S, Ianas O, Vladoiu S, Giurcaneanu M, Ionescu L, Neacsu E, Voicu G, Stoiceanu M, RoscaR, Neamtu C, Badiu C, Dumitrache C

    Does Obesity Protect Postmenopausal Women Against Osteoporosis?

    Acta Endo (Buc) 2012 8(1): 67-76 doi: 10.4183/aeb.2012.67

    Introduction. Obesity was considered to protect against osteoporosis. Recent studies indicate the opposite.\r\nThe study aimed to see if adipose tissue has a protective effect on bone mass and if adipocytokines can explain the\r\nrelationship between obesity and osteoporosis.\r\nSubjects and methods We designed a study enrolling 83\r\npostmenopausal women, aged over 60, without diagnosed or treated osteoporosis and no secondary osteoporosis. We formed 3 groups- group 1- osteoporosis and metabolic syndrome (MetSyn), group 2- osteoporosis, group 3- MetSyn.\r\nWe evaluated the hematological, biochemical profile, bone turnover markers and adipocytokines. DXA of the spine and\r\nthe hip (left) was performed on all the enrolled women. Insulin resistance was appreciated using HOMA index. Metsyn\r\nwas defined using the International Diabetes Federation?s criteria.Results were statistically analyzed using SPSS program, version 15.\r\nResults. All groups were vitamin D insufficient with lower vitamin D, osteocalcin and adiponectin levels in the\r\ngroups with MetSyn and higher leptin levels. BMI correlated positively with spine BMD, while leptin correlated positively with hip BMD, pointing out to the protective effect of obesity against osteoporosis due to leptin?s involvement.\r\nConclusion. Obesity seems to have a protective effect against osteoporosis, probably due to leptin.
  • Editorial

    Coman L, Paunesc H, Catana R, Coman LI, Voiculescu S, Coman OA

    Alzheimer’s Disease – Estrogens and Selective Estrogen Receptor Modulators, Friends or Foes?

    Acta Endo (Buc) 2017 13(1): 77-83 doi: 10.4183/aeb.2017.77

    Alzheimer’s disease(AD) is the leading cause of dementia and is characterized by the presence of extensive plaque deposition and neurofibrillary pathology. The aim of the present study was to make an update regarding the influence of estrogens and SERMs on inflammation and on the resolution of inflammation, respectively, focusing on these most important features implicated in the pathophysiology of AD. Several hypothesised mechanisms of action of estrogens and SERM are exposed and also some relevant clinical studies on this subject are analysed. The analyzed studies have a high heterogeneity of preparations used, of administration routes, of the female population included and of the periods of time from the appearance/ induction of menopause to the therapeutic intervention and also of follow-up periods of patients and of the means of evaluating their cognitive decline. One can say that all the ways of pharmacological influence on the membrane or intracellular signalling system associated to estrogens that may have clinical importance in the prevention and possibly in the treatment of AD have not been exhausted. Estrogens with selective ERα or G protein-coupled estrogen receptors (GPER1 or GqMER) effects could be used to influence the resolution of inflammation process, with positive effects on AD evolution.
  • Obituary

    Voicu V

    Professor Mihail Coculescu MD, FACE, (1943–2016) - Brilliant Continuator of the Romanian School of Endocrinology

    Acta Endo (Buc) 2016 12(2): 123-124 doi: 10.4183/aeb.2016.123

  • Notes & Comments

    Voicu V, Medvedovici A, Miron D, Radulescu F

    A novel approach on pharmacokinetic/pharmacodynamic correlations of risperidone: understanding its safety and efficacy profiles

    Acta Endo (Buc) 2010 6(2): 265-285 doi: 10.4183/aeb.2010.265

    The pharmacokinetic characteristics of a compound as well as the immediate consequences of its physicochemical behavior during interactions with biological structures,\r\nrepresent the key issues for its pharmacodynamic profile, starting from the most fundamental global aspects (i.e. central and / or peripheral action) to the most detailed ones (i.e. molecular mechanism of action).\r\nSuccessive metabolic reactions lead to either bioactivation or bioinactivation of themolecular entity. A particular importance is currently assigned to several molecular\r\nphysicochemical descriptors, for instance the polarity degree (mirroring the changes of partition coefficients and of the permeability of biological structures), and emphasizing on distribution and renal excretion rate.\r\nThe active metabolite (9-hydroxy-risperidone) of the atypical antipsychotic agent risperidone has an increased polar character and, consequently, its pharmacokinetic profile is modified compared to the parent drug: especially the penetration through the bood brain barrier and the efflux pump mediated transport were considered. In this context, the kinetic characteristics and their correlation with the pharmacodynamic properties for the two active\r\nentities, as well as the consequences dealing with the antipsychotic efficacy, the safety and efficacy profiles can be anticipated. The present approach critically asseses the available data from literature corroborated with the personal findings over the last years.
  • Case Report

    Cucu CI, Giurcaneanu C, Mihai MM, Voiculescu VM, Beiu C, Martin S, Negoita S, Popa LG , Miron A

    Hidradenitis Suppurativa in Postmenopause

    Acta Endo (Buc) 2021 17(2): 274-277 doi: 10.4183/aeb.2021.274

    Background. Hidradenitis suppurativa (HS) is a chronic, debilitating disease with a profound impact on the quality of life of patients. Objectives. To describe a rare case of HS with postmenopausal onset, to review the literature data regarding late onset HS and to discuss the current knowledge on the role of endocrine abnormalities in the development of HS. Case report. We report the case of a 68-year-old patient in whom HS occurred 10 years after menopause. She was referred to our clinic for the presence of an open fistula on the left groin, fibrotic scars and visible alteration of the vulvar anatomy due to numerous surgical interventions. The patient shared features of the metabolic syndrome (obesity, arterial hypertension, dyslipidemia, aortic atherosclerosis), but showed no signs of virilism and no hormonal abnormality. HS was controlled using antiseptics, topical retinoids and antibiotics. Conclusions. This case is of particular interest given the late onset of HS, long time after menopause. The development of HS requires a complex interaction between genetic predisposing factors, endocrine dysregulation, metabolic alterations, bacterial overgrowth and an aberrant inflammatory response. Evidence points to an important role of sex-hormones in the emergence and progression of the disease, but the underlying mechanisms are still unclear. A better understanding of HS pathogenesis is needed to elucidate the precise way in which endocrine factors influence the disease onset and course. This would guide the way to novel therapies and a better control of this challenging disease.
  • Perspectives

    Voicu VA

    New National Strategy in Drug Development and Research, Connected to the European Trends

    Acta Endo (Buc) 2013 9(3): 345-348 doi: 10.4183/aeb.2013.345

  • Endocrine Care

    Coculescu M, Anghel R, Trifanescu R, Voicu D, Karavitaki N, Wass JA

    The outcome of macroprolactinomas resistant to dopamine agonists

    Acta Endo (Buc) 2005 1(4): 423-440 doi: 10.4183/aeb.2005.423

    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).
  • Endocrine Care

    Bumbacea RS, Popa LG, Orzan OA, Voiculescu VM, Giurcaneanu C

    Clinical and Therapeutic Implications of the Association between Chronic Urticaria and Autoimmune Thyroiditis

    Acta Endo (Buc) 2014 10(4): 595-604 doi: 10.4183/aeb.2014.595

    Context. Chronic idiopathic urticaria (CIU) is often associated with autoimmune thyroiditis (AT). Objective. The aim of this study was to analyze the clinical particularities of patients with CIU associated with AT and to evaluate the efficacy of dapsone in such patients. Design. We performed an observational study of patients hospitalized in our clinic between January 2010 - December 2013 for moderate/severe chronic urticaria (CU). Subjects and Methods. Data regarding medical history, clinical, paraclinical findings, coexistence of AT and response to treatment were compared between patients with CU and AT and those without AT. Patients continued oral H1 antihistamines. Severe flares required systemic corticotherapy. 11 patients with refractory CIU associated with AT received dapsone treatment. Levothyroxine was administered in patients with hypothyroidism. Results. Among the 210 patients admitted for CU, 39 (92% female) were diagnosed with CIU associated with AT. Patients with CIU associated with AT had a slightly longer disease duration, a higher prevalence of angioedema (25.6% vs. 16.7%) and a more frequent need of systemic corticotherapy for urticaria exacerbations (46.2% vs. 30.4%). All 39 patients achieved significant clinical improvement after a mean period of 4 weeks based on urticaria activity score (UAS) 7 (p<0.0001). Conclusions. Assays for thyroid autoantibodies and thyroid function should be part of the workup in patients with CU, enabling the diagnosis of autoimmune urticaria. Without correction of the underlying autoimmune mechanisms, CU may persist regardless of conventional treatment. Dapsone represents a therapeutic option in autoimmune CU.