Abnormal Sensitivity to Glucagon and Related Peptides in Primary Adrenal Cushing's Syndrome.

Illegitimate G-protein coupled receptors are known to control cortisol secretion in adrenal adenomas and bilateral macronodular adrenal hyperplasias (BMAHs) causing Cushing's syndrome. In the present study, we have evaluated the role of glucagon in the regulation of cortisol secretion in 13 patients with BMAH or adrenocortical adenoma causing subclinical or overt Cushing's syndrome. Injection of glucagon provoked an increase in plasma cortisol in 2 patients. After surgery, immunohistochemical studies showed the presence of glucagon receptor-like immunoreactivity in clusters of spongiocytic cells in adrenal tissues from patients who were sensitive in vivo to glucagon. We also observed an in vitro cortisol response to vasoactive intestinal peptide from an adenoma, which was insensitive to glucagon and pituitary adenylate cyclase-activating peptide. Altogether, our data show that ectopic glucagon receptors are expressed in some adrenal cortisol-producing benign lesions. Our results also indicate that circulating glucagon may influence cortisol release under fasting conditions.

Solitary fibrous tumour of the liver with IGF-II-related hypoglycaemia. A case report.

INTRODUCTION: We report a rare case of solitary fibrous tumour (SFT) of the liver associated with non-islet cell tumour hypoglycaemia (NICTH), which caused a hypoglycaemic coma due to over-production of big-insulin-like growth factor-II. DISCUSSION: Although generally benign, SFTs are better characterised, lately due to Western blot, but less than 40 cases have been reported where the liver is the target organ. In only two benign cases has hypoglycaemia been a feature. CONCLUSION: We report for the first time a demonstrable relationship between benign liver SFT and NICTH.

Hormonal and metabolic effects of radiotherapy in acromegaly: long-term results in 128 patients followed in a single center.

Conventional radiotherapy is usually indicated in acromegaly when surgery fails to normalize GH secretion. However, the benefits of radiotherapy are delayed. This has raised questions about the potency of this treatment for reaching the safe GH level of 2.5 microg/L and for normalizing insulin-like growth factor I (IGF-I) levels, both of which are currently recommended as the therapeutic goal. To evaluate the long-term hormonal and metabolic effects of radiotherapy in acromegaly, a retrospective analysis was undertaken studying 128 patients followed for 11.5+/-8.5 yr (mean +/- SD) in a single center. The preradiation GH levels decreased as a function of time to 50% at 2 yr, 20% at 5 yr, and 10% at 10 yr. Basal GH levels below 2.5 microg/L were obtained in 7% of the patients at 2 yr, 35% at 5 yr, 53% at 10 yr, and 66% at 15 yr. A basal GH level below 2.5 microg/L was associated with suppression of GH below 2 microg/L during an oral glucose tolerance test and normalization of IGF-I levels in 9 of 10 patients. Preradiation GH levels was the sole factor that could predict the delay in GH fall to below 2.5 microg/L (P = 0.008). At the last follow-up, IGF-I levels were normalized in 79% of the patients (37 of 47; mean follow-up, 15.0+/-11.3 yr). In the 32 patients presenting with diabetes mellitus, improvement of glucose tolerance was associated with lower GH levels after treatment (35+/-78 microg/L in the group of 13 patients still presenting diabetes; 9+/-12 microg/L in the group of 4 patients with glucose intolerance; 5+/-8 microg/L in the 14 patients with normal glucose tolerance; P = 0.04). Ten years after termination of radiotherapy gonadotroph, thyreotroph and corticotroph deficiencies were observed in 80%, 78%, and 82% of the patients, respectively. In conclusion, conventional radiotherapy can reduce GH levels below the optimal level of 2.5 microg/L and normalize IGF-I levels in acromegaly. However, the incidence of late hypopituitarism is high, and the delay to obtain this safe GH secretory status can be long, depending on the preradiation GH level. These parameters should be considered when adjuvant therapy is needed after surgery.

[Failure of synthcen to diagnose corticotropin insufficiency]. / Pièges de l'épreuve au synacthène immédiat dans l'insuffisance corticotrope.

It is commonly believed that a normal cortisol response to exogenous ACTH (synacthen test) reliably indicates, with the exception of states of acute ACTH deprivation, the integrity of hypothalamic-pituitary-adrenocortical function. Published evidence has shown that the synacthen test is not sensitive enough to reveal partial ACTH deficiency leading to a subnormal ACTH response to stress. We report a patient who maintained a normal response to exogenous ACTH stimulation despite symptomatic chronic ACTH deficiency in unstressed conditions. A normal cortisol response in the synacthen test does not therefore exclude the possibility of clinically relevant ACTH deficiency.

[Struma ovarii or malignant ovarian goiter. A case]. / Les struma ovarii ou goitres ovariens malins. Une observation.

BACKGROUND: We report a case of follicular struma ovarii observed in an ovary teratoma without metastatic dissemination. CASE REPORT: A right ovarian tumor was discovered at ultrasound examination in a 31-year-old woman complaining of low abdominal pain. The patient underwent laparoscopic exploration and a 4-cm cystic mass of the right ovary was removed. Microscopic examination showed a malignant struma ovarii of the follicular type with vascular space invasion; other teratomous elements were identified. Immunohistochemical staining for thyroglobulin confirmed the nature of the tumor. The patient was treated by complete right ovariectomy followed by total thyroidectomy and administration of radioactive iodine (99 mCi I-131). Repeat I-131 body scan performed at 6 months was normal. DISCUSSION: Struma ovarii is a rare type of ovarian teratoma, consisting mainly of thyroid tissue. The incidence of malignant struma ovarii is below 1% and fewer than two dozen cases with distant metastases have been reported. The major problem associated with struma ovarii has been the establishment of criteria for malignancy.

[Differentiated thyroid carcinomas manifesting as toxic adenoma]. / Carcinomes thyroïdiens différenciés se manifestant comme un adénome toxique.

BACKGROUND: Hot thyroid nodules are generally benign. We report two exceptional cases of thyroid carcinomas mimicking toxic adenomas. CASE REPORTS: A 35-year-old man and a 55-year-old woman had thyroid carcinoma behaving as an autonomously hyperfunctioning nodule. DISCUSSION: Only twenty similar cases have been reported in the literature. While a hot nodule on radio-iodine scan is unlikely to be malignant, the possibility of carcinoma should not be overlooked. Surgery should therefore be the preferred treatment of toxic adenoma.

[Granular cell tumors. Rare tumors of the neurohypophysis]. / Les tumeurs à cellules granuleuses. Des tumeurs rares de la neurohypophyse.

Granular cell tumours of neurohypophysis are rare. These tumours are more often encountered as incidental autopsy findings seen in up to 17% of unselected adult autopsy cases. There are few reports of parasellar granular cell tumours large enough to cause symptoms. We present three cases of neurohypophysis granular cell tumour and a review of the literature. In one patient, the asymptomatic granular cell tumour was incidentally discovered at surgical removal of a corticotroph microadenoma. The remaining 2 patients had a symptomatic tumour which caused neurological symptoms such as visual disturbance and headaches and endocrine disorders such as hypopituitarism or hyperprolactinaemia. In these 2 cases, computerized tomography showed a well-circumscribed, contrast-enhanced, intrasellar and suprasellar mass. Magnetic resonance imaging demonstrated an isointense gadolinium-enhanced mass in T1-weighted images. Transsphenoidal partial resection was performed and histology was interpreted as a granular cell tumour. The immunohistochemical study was positive for glial fibrillary acidic protein (GFAP) and neuron specific enolase (NSE) in 1 of the 2 tumours and positive for S100 protein and vimentin in both tumours but negative for CD68. The histogenesis of neurohypophysis granular cell tumours is still controversial but ultrastructural and immunohistochemical studies support the theory that they may arise from pituicytes, the glial cells of neurohypophysis. Management of these benign, slow-growing, tumours is based mainly on neurosurgical resection. Data from the literature do not support a beneficial effect of postoperative radiation therapy on postoperative recurrences.

Stimulatory effect of gonadotropin-releasing hormone (GnRH) on in vitro prolactin secretion and presence of GnRH specific receptors in a subset of human prolactinomas.

The purpose of this study was to determine whether gonadotropin-releasing hormone (GnRH) may exert a direct action on human prolactinomas. On a series of 17 adenomas, we studied the effect of GnRH on the in vitro prolactin (PRL) secretion of dispersed and perifused cells of 10 cases and the [125I]GnRH agonist binding on frozen sections of three out of the adenomas studied in perifusion and on the membrane preparations of seven other cases. Two 20-min pulses of GnRH (10(-7) mol/l) stimulated the in vitro PRL secretion of three adenomas out of 10 (increase of 200, 444 and 205%, respectively, above basal levels). The GnRH receptors of three adenomas bound GnRH agonist (Des-Gly10-(D-Ala6)-GnRH ethylamide). The binding was specific, with a high affinity (Kd = 0.60, 0.48 and 0.40 nmol/l) similar to that of two human anterior pituitaries obtained post-mortem (Kd = 0.70 and 0.40 nmol/l). Indirect immunoperoxidase revealed that the majority of the cells (60-90%) in all the adenomas studied contained immunoreactive PRL. Four of them also contained cells immunoreactive to the alpha-subunit of the glycoprotein hormones. In none of the prolactinomas were cells immunoreactive to antiserum of anti-beta-luteinizing hormone, anti-beta-follicle-stimulating hormone or anti-beta-thyrotropin. All the prolactinomas that were responsive to GnRH in perifusion experiments and/or bound specifically to [125I]GnRH agonist were also immunoreactive for alpha-subunit. These results show that GnRH, via GnRH specific receptors, exerts a stimulation on in vitro PRL secretion in a subset of prolactinomas characterized by the presence of alpha-subunit.