Ronald Comtois

The clinical and endocrine outcome to trans-sphenoidal microsurgery of nonsecreting pituitary adenomas

From 1962 to 1987, 126 patients underwent trans‐sphenoidal surgery for primary treatment of pituitary adenomas unassociated with clinical or biochemical evidence of hormonal overproduction. There were 73 male and 53 female patients (mean age, 50 ± 12 years). Before surgery, 56% of the patients (70 of 124) had headaches, 74% (94 of 126) had deterioration of vision, and 12% (15 of 126) had ophthalmoplegia. Endocrine evaluation revealed the presence of hypogonadism in 75% (87 of 115), adrenal insufficiency in 36% (46 of 126), and hypothyroidism in 18% (21 of 122). Plasma prolactin was increased in 65% (56 of 86) with a mean level of 39 ± 14 μg/l (normal, 3 to 20 μg/l). Radiologic enlargement of the sella turcica was documented in all cases: 67% (84 of 126) had enclosed and 33% (42 of 126) had invasive adenomas. After surgery, vision was normalized or improved in 75% (71 of 94) of the patients. Thyroid, adrenal, and gonadal functions were improved in 14% (three of 22), 41% (19 of 46), 11% (ten of 87), were unchanged in 82% (100 of 122), 77% (97 of 126), 89% (102 of 115), and worsened in 15% (19 of 22), 8% (ten of 126), 3% (102 of 115), respectively. Permanent diabetes insipidus occurred in 5% (seven of 126). Two patients died during the immediate postoperative period. The recurrence rate in patients with a mean follow‐up of 6.4 ± 4.2 years was 21% (15 of 71). These data indicate that trans‐sphenoidal microsurgery is an effective and safe initial treatment for patients with nonsecreting pituitary adenoma and may reverse hypopituitarism.

Surgical management of giant pituitary adenomas.

During the past 25 years, 77 giant pituitary adenomas have been treated surgically, including suprasellar extensions of type C in 66 cases and of type D in 11 cases. Non-secreting adenomas were present in 53 and secreting adenomas in 24 cases. All patients except 3 presented with significant visual field defects; including bitemporal hemianopia, superior quadranopia or unilateral temporal hemianopia, contralateral blindness in 73% of the cases, and one case with sudden bilateral blindness due to acute pituitary apoplexy. A single transsphenoidal procedure was carried out in 74% of the patients while 11 patients (7%) required re-operations for recurrent or residual tumor. Only 3 patients required a subsequent transcranial procedure. Complications included 1 CSF-leak, 1 empty-sella syndrome and 4 fatal post-operative hematomas. We prefer the transsphenoidal route even in very large or giant pituitary adenomas, since it allows rapid and adequate decompression of the optic nerves and chiasm, avoids major pituitary insufficiency in 60% of the cases and is associated with low morbidity-mortality rates.

High prolactin levels may be missed by immunoradiometric assay in patients with macroprolactinomas.

OBJECTIVE Large amounts of antigen may produce falsely low values in immunoradiometric assays due to the so‐called high dose, hook effect. The study was designed to identify the clinical and biochemical features of patients with pituitary macroadenomas in whom a high dose PRL hook effect was documented.

Clinical usefulness of estimation of serum fructosamine concentration as screening test for gestational diabetes

Serum fructosamine levels and fructosamine/protein ratios were measured in 100 pregnant women who underwent glucose tolerance tests because of clinical risk. Compared with normal pregnant women, the 13 study participants with gestational diabetes had higher fructosamine/protein levels (39 ± 3.9 μmol/gm versus 37 ± 3.2 μmol/gm, p p −1 versus 22 ± 3.6 gm × min × dl −1 , p r = 0.72, p r = 0.72, p r = 0.58, p r = 0.57, p

High prolactin levels in patients with Cushing's disease without pathological evidence of pituitary adenoma

OBJECTIVE This study was designed to compare the clinical and biochemical features of patients with Cushings disease without pathological evidence of pituitary adenoma (n= 11) to those in whom a pituitary ACTH adenoma was documented (n= 11).

DISTINCTIVE FEATURES OF PROLACTIN SECRETION IN ACROMEGALIC PATIENTS WITH HYPERPROLACTINAEMIA

We have investigated the relationship between the plasma PRL concentrations of 98 untreated acromegalic patients and the GH levels during basal and dynamic conditions. Hyperprolactinaemia was present in 27 patients. In patients with marked hyperprolactinaemia (PRL > 80 ng/ml or > 1600 mU/l), basal plasma PRL and the TRH‐induced response correlated with basal plasma GH (correlation coefficients of 0‐9, P < 0 001 and 0‐74, P <0 02, respectively). The PRL response to TRH also correlated with GH response to TRH (r= 0 38, P <0 01). In contrast, in patients with moderately elevated PRL (20 to 80 ng/ ml), and in those with normal plasma PRL (< 20 ng/ml or < 400 mU/1), no such correlations were found. Immunostaining for PRL was positive in 24 out of 25 adenomas of patients with hyperprolactinaemia, while no PRL was found in the tumour tissue of 10 normoprolactinaemic patients. In conclusion, our data suggest the existence of two populations of acromegalic patients with hyperprolactinaemia, one group with correlations between GH and PRL secretion, and the other without.

Technical and clinical evaluation of fructosamine determination in serum

We evaluated a serum fructosamine (glycated serum proteins) assay for efficacy in the diagnosis and follow-up of diabetic patients. A Roche reagent kit, based on nitroblue tetrazolium reduction in alkaline medium, was used in COBAS FARA centrifugal analyzer. We demonstrated that this method is precise, linear and unaffected by serum hemolysis. However, bilirubin affected the test positively and lipemia negatively. Fructosamine (F) correlated positively with total protein (P) (r = 0.809) and albumin (r = 0.746) in a group of 48 non-diabetic individuals. A good correlation was observed between F and glycated hemoglobin from the sera of 514 patients (r = 0.794). A better correlation (r = 0.838) was obtained when F was corrected for P concentration (F/P). Different F and F/P means were calculated only in patients with overt diabetes, compared to normals. Gestational diabetes was associated with a highly significant F increase. However, its low sensitivity (21%) precludes the use of F as an effective screening test for that condition. Nevertheless, because of its simplicity, low cost and rapidity in reflecting changes in the metabolic control of diabetes, F should be considered a valuable test to assess glycemic control in diabetic patients.

Growth hormone rebound after cessation of sms 201-995 treatment in acromegaly.

We studied a 42-year-old woman who had persistent active acromegaly despite conventional therapies. She was treated for 6 months with SMS 201-995. Her mean plasma growth hormone GH values decreased during treatment from 9.1 +/- 1.2 to 6.6 +/- 1.2 micrograms/L. One month after the withdrawal of SMS 201-995, the plasma GH level increased to 24.4 micrograms/L (P less than 0.001). This elevation was clinically silent and transitory, as GH levels decreased 8 months later to 6.9 +/- 1.3 micrograms/L. Furthermore, at the beginning of therapy, her intractable headache was completely relieved; however, it progressively resumed under therapy. In conclusion, cessation of SMS 201-995 may be followed in some acromegalic patients by a rebound of plasma GH levels. This rebound suggests that SMS 201-995 decreases GH levels by an inhibition of its release from the pituitary. Furthermore, SMS 201-995 may relieve intractable headache in some acromegalic patients, but tolerance to the analgesic effect may develop.

Clinical usefulness of high-pressure liquid chromatographic determination of serum pentamidine in AIDS patients.

We have developed a reproducible HPLC method to determine serum pentamidine, which demonstrates good chromatographic performance, and is sensitive enough to measure therapeutic doses. Pentamidine is first extracted from serum by passage through a C-18 extraction cartridge. Potential interfering substances are then removed by washing with 100% methanol. Pentamidine is eluted from the extraction cartridge with 1-heptanesulfonic acid. The extract is chromatographed on a highly deactivated column for basic compounds in the presence of minimal concentrations of 1-heptanesulfonic acid as the pairing agent. Detection is by fluorescence. The method can determine serum pentamidine levels in the range of 15-600 ng/mL free of interference from other drugs. In monitoring pentamidine levels in AIDS patients with Pneumocystis carinii, we found that trough serum levels over 100 ng/mL were associated with toxicity (hypoglycemia or azotemia) in 100% of patients. With levels under 100 ng/mL, signs of toxicity were observed in only 29% of the patients. We conclude that dose adjustment based on serum levels reduces the incidence of toxicity and enhances pentamidine therapy.

Hypersecretion of gonadotropins by a pituitary adenoma: pituitary dynamic studies and treatment with bromocriptine in one patient

Pituitary adenomas secreting gonadotropins are often diagnosed as nonsecreting tumors on the basis of clinical findings. We now describe a middle-aged woman who developed visual disturbances and was found to have a large infiltrating pituitary adenoma secreting large quantities of follicle-stimulating hormone (FSH) with moderate elevation of luteinizing hormone (LH). The patient twice underwent transsphenoidal microsurgery to partially remove the adenoma. Thereafter, a trial with bromocriptine was initiated. Normal levels of FSH and LH were observed after 6 weeks of treatment as well as improvement of visual field examination. This case illustrates the fact that some gonadotropin-secreting adenomas can be extremely sensitive to dopamine agonist adenomas can be extremely sensitive to dopamine agonist therapy.