[Role of perioperative biological tests during the performance and follow-up of corticotroph adenoma exeresis]. / Place des examens biologiques peropératoires dans la réalisation et le contrôle de l'exérèse des adénomes corticotropes.

ACTH assay in cavernous sinus samples during resection of pituitary adrenocorticotroph adenomas is a simple and safe technique providing an intraoperative assessment of adrenocorticotroph hormone gradients. Bilateral puncture of the cavernous sinus can be achieved vial the standard transsphenoidal approach to the sella turcica. ACTH is determined with IRMA at 37;C with an incubation time of less than one hour. Among 71 cases in our experience, the ACTH gradient accurately predicted the position of the adenoma in 93% of the cases. This rate is higher than the 61% accuracy reported for inferior petrosal sinus sampling. The technique reported is more precise than MRI which correctly identifies adenomas in only 50% of the cases. The remaining cases are either false positives or false negatives. We report an 82% cure rate either via direct resection of the microadenoma or via partial hypophysectomy guided by the ACTH gradient. In our series, 20 cases of Cushing's disease had a normal MRI and no surgically identifiable adenoma. In 10 of these cases however, cure was achieved by performing ACTH gradient guided partial hypophysectomy. This method produces no morbidity and is most helpful for the neurosurgeon allowing confirmation of the position of an MRI-visible adenoma or an adenoma identified intraoperatively. It does not however replace neurosurgical experience which remains the most important predictive factor for outcome in surgical treatment of Cushing's disease.

Cushing's syndrome due to a gastric inhibitory polypeptide-dependent adrenal adenoma: insights into hormonal control of adrenocortical tumorigenesis.

We studied a patient with food-induced, ACTH-independent, Cushing's syndrome and a unilateral adrenocortical adenoma. In vivo cortisol secretion was stimulated by mixed, glucidic, lipidic, or proteic meals. Plasma ACTH levels were undetectable, but iv injection of ACTH stimulated cortisol secretion. Unilateral adrenalectomy was followed by hypocortisolism with loss of steroidogenic responses to both food and ACTH. In vitro, cortisol secretion by isolated tumor cells was stimulated by the gut hormone gastric inhibitory polypeptide (GIP) and ACTH, but not by another gut hormone, glucagon-like peptide-1 (GLP-1). Both peptides stimulated the production of cAMP but not of inositol 1,4,5-trisphosphate. In quiescent cells, GIP and ACTH stimulated [3H]thymidine incorporation and p42-p44 mitogen-activated protein kinase activity. GIP receptor messenger ribonucleic acid (RNA), assessed by RT-PCR, was highly expressed in the tumor, whereas it was undetectable in the adjacent hypotrophic adrenal tissue, in two adrenal tumors responsible for food-independent Cushing's syndrome, and in two hyperplastic adrenals associated with ACTH hypersecretion. In situ hybridization demonstrated that expression of GIP receptor RNA was confined to the adrenocortical tumor cells. Low levels of ACTH receptor messenger RNA were also detectable in the tumor. We conclude that abnormal expression of the GIP receptor allows adrenocortical cells to respond to food intake with an increase in cAMP that may participate in the stimulation of both cortisol secretion and proliferation of the tumor cells.

[Role of hormonal exploration in avoiding of the failures of anterior pituitary gland surgery in Cushing disease]. / Rôle de l'exploration hormonale dans l'esquive des échecs de la chirurgie anté-hypophysaire de la maladie de Cushing.

Patients with Cushing's disease are not cured by transsphenoidal microsurgery in about 30% of the cases. Beside the problem of invasive macroadenomas, these failures are due either to diagnostic errors, or to very small microadenomas that could no be found. Positive diagnosis of hypercortisolism is quite straightforward and the problem is sensitivity rather than specificity. Primary adrenocortical hypercortisolism should not be mistaken. Depression-related hypercortisolism can be difficult to distinguish from Cushing disease: most cases are recognized after clinical story and CRF stimulation test. Ectopic ACTH secretion by a carcinoid tumor represents at least 8% of ACTH-dependant hypercortisolism. It cannot be reliably distinguished from corticotroph microadenoma by either classical dynamic tests or anterior pituitary imaging. However measurements of ACTH in the inferior petrosal sinus under basal condition and CRF stimulation allow the diagnosis of central or peripheral ACTH secretion with a quasi 100% sensitivity and specificity. In contrast this technique is of poor help for the diagnosis of lateralization of corticotroph microadenomas, for which it gives erroneous results in 25 to 50% of the cases. Rapid intraoperative measurement of ACTH in peripituitary blood seems a more reliable approach. In our series it gave correct results in 11 out of 12 cases. In 1995 hormonal exploration of Cushing disease should limit the failures of anterior pituitary surgery to the cases of invasive macroadenomas that cannot be completely removed.

[Catheterization of the inferior petrosal sinus. Its role in the diagnosis of Cushing's syndrome. Experience with 23 explorations]. / Le cathétérisme des sinus pétreux inférieurs. Sa place dans le diagnostic du syndrome de Cushing. Expérience de 23 explorations.

Selective catheterization of the inferior petrosal sinus has been performed in 23 patients: 11 Cushing's disease, 5 lung carcinoid tumors whose diagnosis has been confirmed by surgery and 7 ACTH-dependent hypercortisolism whose final diagnosis has not yet been proved. The pituitary origin of hormone secretion is accepted if the central-to-peripheral ratio (C/PR) is equal or greater than 2 on basal values and/or during CRF test. On basal values, all subjects but one with confirmed pituitary lesions exhibited a C/PR > or = 2; the carcinoid tumors never exceeded the value of 1.3. After CRF injection, all the pituitary tumors showed an increase in C/PR; one patient with a lung carcinoid tumor (CRF-negative) showed a pituitary ACTH secretion (C/PR = 3.7). The localization of pituitary adenoma by the lateralization of hormone secretion is disappointing, except, perhaps, for very small extremely lateral adenomas. No accident occurred in our series, nor in the literature. This investigation seems the most reliable approach to prove the pituitary origin of hormonal hypersecretion. We recommend it to be performed in ACTH-dependent Cushing's syndrome when the secretory pattern is not typical and/or pituitary imaging is normal.

Insulin sensitivity in zinc-depleted rats: assessment with the euglycaemic hyperinsulinic clamp technique.

The present knowledge about zinc deficiency and insulin-sensitivity is not yet established. Using three groups of rats fed zinc-depleted diet (ZD) zinc adequate diets, either Pair Fed or ad libitum for a six weeks period, we measured the glucose turn over by the euglycaemic hyperinsulinaemic clamp technique coupled with tritiated glucose as tracer. The basal hepatic glucose production (HGP) and insulinaemia were lower in zinc-depleted rats. At a low rate of insulin infusion (0.6 mU/min/rat) the zinc-depleted rats did not show any difference in hepatic insulin sensitivity compared with the pair-fed animals. At high level of insulin rate (3 mU/min/rat; 9 mU/min/rat), the zinc-depleted rats exhibited a lower glucose uptake compared to the two control groups (Pair-fed and Ad libitum animals). This peripheral insulin resistance is therefore related to a modification of insulin receptors, or post receptors events in zinc deficiency.