Alessandra Casagrande

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.

Ensaios para a medida de hormônio do crescimento (GH) e IGF-I: aspectos metodológicos e suas implicações no diagnóstico e seguimento da acromegalia

ABSTRACT Growth Hormone (GH) and IGF-I Assays: Methodological Aspectsand its Implications in Acromegaly Diagnosis and Follow-Up.Growth hormone quantification in serum is essential for confirming or rul-ing out its excess. The absence of clinical criteria sufficiently sensitive toevaluate the treatment success enables GH as the key diagnostic proce-dure and for that, its measurements must be done in a reliable way andmust allow uniform interpretation. Several different biochemical criteriafor remission have been suggested in the past, including a random GHmeasurement less than 2.5 µg/l, mean GH value from a day curve less than2.5 µg/l, nadir GH value after an oral glucose tolerance test (OGGT) lessthan 1.0 µg/l and a normal age-related IGF-I level. The importance of ade-quate treatment is highlighted by data indicating that lowering GH levelsto less than 2.5 µg/l reverses the premature mortality of acromegaly. Withthe advances of ultrasensitive assays for GH measurement, strictest remis-sion criteria to determine remission or cure were necessary. In this review,we describe the changes of assay methodology and its consequences inserum GH results and cut off point values to define activity and remissionof acromegaly. (Arq Bras Endocrinol Metab 2007;51/4:511-519)Keywords: Growth hormone; Diagnosis; Acromegaly; Immunoassays

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.