Guilherme Alcides Flores Soares Rollin

Prospective Evaluation of Transsphenoidal Pituitary Surgery in 108 Patients with Cushing's Disease

Transsphenoidal pituitary surgery (TSS) remains the treatment of choice for Cushings disease (CD). Despite the widespread acceptance of this procedure as the first line treatment in CD, the indication of a second TSS in not cured or relapsed DC patients is not consensus. We report the results of TSS in 108 patients with CD (a total of 117 surgeries). The mean postoperative follow-up period was 6 years. Remission was defined as clinical and laboratorial signs of adrenal insufficiency, period of glucocorticoid dependence, serum cortisol suppression on oral 1-mg dexamethasone overnight suppression test and clinical remission of hypercortisolism. We evaluated 103 patients with CD by the time of the first TSS. Fourteen patients underwent second TSS (5 had already been operated in others centers; in 5 patients the first surgery was not curative; in 4 patients CD relapsed). Remission rates were 85.4% and 28.6% (p < 0.001) after first and second TSS, respectively. In microadenomas, remission rates were higher than macroadenomas (94.9% vs. 73.9%; p = 0.006). In patients with negative pituitary imaging remission rates were 71.4% (p = 0.003; vs. microadenomas). Postoperative complications were: transient diabetes insipidus, definitive diabetes insipidus, hypopituitarism, stroke and one death. Only hypopituitarism was more frequent after second TSS (p = 0.015). In conclusion, TSS for CD is an effective and safe treatment. The best remission rates were observed at the first surgery and in microadenomas. The low remission rates after a second TSS suggest that this approach could not be a good therapeutic choice when the first one was not curative.O tratamento de escolha para a doenca de Cushing (DC) ainda e a cirurgia transesfenoidal (CTE) para resseccao do adenoma hipofisario produtor de ACTH. Porem, a indicacao de uma segunda CTE representa uma questao controversa, tanto nos pacientes nao curados apos a primeira cirurgia quanto nos casos de recidiva. Neste trabalho, relatamos os resultados da CTE em 108 pacientes com DC (totalizando 117 cirurgias). O tempo medio de seguimento foi de 6 anos. Criterios de cura: ocorrencia de insuficiencia adrenal (clinica ou laboratorial), periodo de dependencia ao glicocorticoide, supressao do cortisol serico pos-1 mg de dexametasona overnight e remissao clinica do hipercortisolismo. Foram avaliados 103 pacientes com DC submetidos a primeira CTE. Quatorze pacientes foram submetidos a uma segunda CTE (5 ja tinham sido operados em outros centros; a primeira cirurgia nao fora curativa em 5; 4 pacientes com recidiva da DC). Indices de cura: 85,4% e 28,6% (p < 0,001) apos a primeira e segunda CTE, respectivamente. Nos microadenomas, remissao maior que nos macroadenomas (94,9% vs. 73,9%; p = 0,006). Nos pacientes com imagem hipofisaria negativa, cura foi de 71,4% (p = 0,003; vs. micro). Complicacoes pos-operatorias: diabetes insipidus transitorio e definitivo, hipopituitarismo, acidente vascular cerebral e um obito. Apenas a ocorrencia de hipopituitarismo foi mais frequente apos a segunda CTE (p = 0,015). Assim sendo, a CTE para a DC representa uma terapeutica efetiva e segura. Os melhores indices de cura foram obtidos na primeira cirurgia e em microadenomas. O baixo indice de cura apos a segunda CTE sugere que esta abordagem nao deve ser considerada uma boa opcao terapeutica quando a primeira cirurgia nao for curativa.

Evaluation of Cushing's disease remission after transsphenoidal surgery based on early serum cortisol dynamics

To evaluate the ability of post‐transsphenoidal pituitary surgery (TSS) serum cortisol levels (s‐cortisol) to predict surgical remission and recurrence of Cushings disease (CD).

Criteria of Cure and Remission in Cushing's Disease: An Update

We review the clinical and biochemical criteria used for evaluation of the transsphenoidal pituitary surgery results in the treatment of Cushings disease (CD). Firstly, we discuss the pathophysiology of the hypothalamic-pituitary-adrenal axis in normal subjects and patients with CD. Considering the series published in the last 25 years, we observed a significant variation in the remission or cure criteria, including the choice of biochemical tests, timing, threshold values to define remission, and the interference of glucocorticoid replacement or previous treatment. In this context we emphasize serum cortisol levels obtained early (from hours to 12 days) in the postoperative period without any glucocorticoid replacement or treatment. Our experience demonstrates that: (i) early cortisol < 5 to 7 microg/dl, (ii) a period of glucocorticoid dependence > 6 mo, (iii) absence of response of cortisol/ACTH to CRH or DDAVP, (iv) return of dexamethasone suppression, and circadian rhythm of cortisol are appropriate indices of remission of CD. In patients with undetectable cortisol levels early after surgery, recurrence seems to be low. Finally, although certain biochemical patterns are more suggestive of remission or surgical failure, none has been proven to be completely accurate, with recurrence observed in approximately 10 to 15% of the patients in long-term follow-up. We recommended that patients with CD should have long-term monitoring of the CRH-ACTH-cortisol axis and associated co-morbidities, especially hypopituitarism, diabetes mellitus, hypertension, cardiovascular disturbances, and osteoporosis.

Effects of oral and transdermal estrogen on IGF1, IGFBP3, IGFBP1, serum lipids, and glucose in patients with hypopituitarism during GH treatment: a randomized study

OBJECTIVE To evaluate the effects of oral estradiol and transdermal 17β-estradiol on serum concentrations of IGF1 and its binding proteins in women with hypopituitarism. DESIGN Prospective, comparative study. METHODS Eleven patients with hypopituitarism were randomly allocated to receive 2 mg oral estradiol (n=6) or 50 μg/day of transdermal 17β-estradiol (n=5) for 3 months. RESULTS The oral estrogen group showed a significant reduction in IGF1 levels (mean: 42.7%±41.4, P=0.046); no difference was observed in the transdermal estrogen group. There was a significant increase in IGFBP1 levels (mean: 170.2%±230.9, P=0.028) in the oral group, but not in the transdermal group. There was no significant difference within either group in terms of median IGFBP3 levels. In relation to lipid profiles, there was a significant increase in mean high-density lipoprotein cholesterol levels in the oral group after 3 months of treatment, (27.8±9.3, P=0.003). We found no differences in the anthropometric measurements, blood pressure, heart rate, glucose, insulin, C-peptide, or the homeostasis model assessment index after treatment. CONCLUSIONS Our preliminary data indicate that different estrogen administration routes can influence IGF1 and IGFBP1 levels. These findings in patients with hypopituitarism have an impact on their response to treatment with GH, since patients receiving oral estrogen require increased GH dosage. These results suggest that oral estrogens may reduce the beneficial effects of GH replacement on fat and protein metabolism, body composition, and quality of life.

Evaluation of the DDAVP test in the diagnosis of Cushing's Disease

To analyse the performance of the desmopressin (DDAVP) test in the diagnosis of Cushings disease (CD).

Avaliação do eixo hipotálamo-hipófise adrenal no diagnóstico e na remissão da doença de Cushing

Cushings disease (CD) remains a medical challenge, with many questions still unanswered. Successful treatment of CD patients is closely related to correct approach to syndromic and etiological diagnosis, besides the experience and talent of the neurosurgeon. Pituitary transsphenoidal adenomectomy is the treatment of choice for DC. Assessment of remission after surgery and recurrence in the long term is an even greater challenge. In this regard, special attention should be paid to the role of postoperative serum cortisol as a marker of CD remission. Additionally, the postoperative use of exogenous glucocorticoids only in cases of adrenal insufficiency has been suggested by some authors as an essential practice to enable the use of serum cortisol in this scenario. In this article, we review the forms of evaluation of DC activity, and markers of remission and relapse of CD after transsphenoidal surgery.

Síndrome de Cushing: é possível simplificar e padronizar sua abordagem diagnóstica?

The diagnosis of Cushings syndrome require an accurate clinical suspicion, information about hypothalamic-pituitary-adrenal axis, adequate use of functional hormonal tests and the indication of resolutive image examination with the objective of determining its etiology. In this paper, we discuss the diagnostic approach of the Cushings syndrome, the application of the hormonal tests used for the syndromic and etiologic definition, with special focus in the differential diagnosis of Cushings Disease vs. pseudo-Cushings states and Cushings disease vs. ectopic ACTH syndrome. Finally, we propose a standard approach for these patients, including suggestions about the application of sophisticated and invasive methods.

A successful case of Cushing's disease pregnancy treated with ketoconazole

Abstract Purpose: The association of pregnancy and Cushings disease (CD) is rare. Treatment of Cushings syndrome (CS) is imperative to reduce maternal and fetal morbidity. Ketoconazole is a widely used drug for CS control when the woman is not pregnant but concerns about its teratogenicity and embryotoxicity restricted its use during pregnancy. Methods and results: We describe a case of a CD patient managed with Ketoconazole during the first and second trimester and other cares for her metabolic CS aspects during pregnancy. She delivered a normal female baby. Conclusions: It is supposed that even with treatment the relatively hypercortisolemic mother could protect her child from the embryotoxicity of ketoconazole as proved in rat fetuses and we suggest that ketoconazole could be an emergency pharmacological therapeutic option for CS management during pregnancy.

Utilização da insulina glargina em crianças menores de oito anos de idade

OBJECTIVES: To evaluate prospectively the efficacy and safety of insulin glargine use for the metabolic control of type 1 diabetes mellitus (T1DM) children younger than eight years old. METHODS: Nineteen boys and 11 girls with T1DM were included. Before initiating insulin glargine, all children received intensive NPH and aspart insulins for three months. Afterwards, they were assisted for 12 more months for glargine treatment. All patients performed self blood glucose monitoring before and two hours after meals and in early morning (3:00 AM). Primary endpoints: metabolic control using A1C levels; frequency of mild hypoglycemia (capillary glycemia < 60 mg/dL); and frequency of severe hypoglycemia (loss or alteration of consciousness, seizures or need for medical intervention). RESULTS: Mean A1C at the study entry was 8.68% and after 12 months of glargine, was 8.64% (p = 0.82). Frequency of mild hypoglycemia at 3.00 AM was 1.43/3 months during the NPH period and 0.28/3 months during the glargine period (p < 0.007). Frequency of severe hypoglycemia was 0.56/3 months during the NPH period and 0.008/3 months during the glargine period (p < 0.002). CONCLUSIONS: The treatment of T1DM children with insulin glargine was considered as efficacious as with NPH. However, a better safety profile, disclosed by the lower incidence of nocturnal and severe hypoglycemia episodes, was observed for insulin glargine.

Tumores não hipofisários da região selar

The pituitary gland, sella turcica and the parasellar region can be involved by a wide variety of lesions, including benign and malignant neoplasms as well as a wide variety of non neoplastic tumor-like lesions. Clinical and radiological aspects could help in the differential diagnosis of these lesions. Nevertheless, in many cases only the histopathological analysis could establish the definitive diagnosis. In this paper, we review the nonpituitary tumors of the sellar region emphasizing the associated hormonal disturbances.