Faculty Bibliography

The GHRH test may represent a new tool in the study of GH dynamics in acromegaly. GH responsiveness to GHRH 1-40 (50 micrograms iv) has been studied in 21 acromegalic patients. Nineteen out of 21 had active disease. Five patients were also studied 1-12 months after neurosurgery. Two apparently cured acromegalics were studied 1-2 yr after surgery. GH secretion has been evaluated in all patients by means of TRH, bromocriptine and insulin hypoglycemia tests, too. GH response to GHRH has also been performed in 14 normal subjects. In acromegaly, GH responses after GHRH (p less than 0.01 vs placebo) were variable. The GH peak ranged from 8 to 445 ng/ml in patients with active disease. Maximum GH increase after GHRH (calculated as peak/basal value ratio) was significantly reduced in acromegaly (2.9 +/- 0.5 ng/ml; mean +/- SE) in comparison to controls (34.1 +/- 10.9 ng/ml; p less than 0.01). No significant differences in GH pattern after GHRH were found between untreated and previously treated patients with active disease. A significant correlation was found between GH basal levels and GH incremental area (p less than 0.05) and between GH basal and peak levels (p less than 0.01) after GHRH. A significant increase in PRL secretion was observed in acromegalic patients after GHRH (p less than 0.01 vs placebo). No discernable variation was found in the other pituitary hormones pattern after the peptide administration. A positive correlation was observed between GH increase after GHRH and insulin hypoglycemia (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

GRF (1-40), dopamine (DA), DA plus GRF and placebo were administered to 6 acromegalic patients. The GRF administration induced a highly variable GH release (GH delta % 167.3 +/- 21.4; mean +/- SE). GRF did not provoke any change in PRL serum levels. During simultaneous GRF and DA administration GH release was found to be reduced (GH delta % 80.2 +/- 17.8) compared to that observed for a corresponding period of time after GRF alone (p less than 0.05). Our data underscore that in acromegaly the DA tonus inhibits GH secretion after GRF by acting directly at the pituitary level.

In eight normal adult men pituitary secretion following GRF(1-40) was studied. GRF administration (50 micrograms i.v.) was followed by an increase in GH release with a peak value between the 15 and 60 min. No effects were noticed on LH, FSH, PRL, TSH and ACTH secretion. GH and PRL release was also studied after domperidone (DOM) (5 mg i.v./h), and GRF plus DOM. PRL increased significantly after DOM and GRF plus DOM. During GRF plus DOM a more marked GH release was observed in comparison with the hormone response to GRF alone at 15-45 and 120 min (P less than 0.05). This phenomenon was found in in six out of eight subjects studied. Mean peak and secretory area was greater (P less than 0.05) after GRF plus DOM than after GRF alone. These data suggest that GRF(1-40) at the dose used is a useful tool in the study of GH secretion. The GH pattern during GRF plus DOM seems to indicate that dopaminergic tone may play a direct inhibitory role on GH secretion in man.

Fasting and hypocaloric diets are known to induce a reduction of triiodothyronine (T3) and to increase reverse triiodothyronine (rT3) in normal and obese subjects. The effect of 8-day fasting was evaluated on T3, thyroxine (T4), free T4, rT3, TSH, immunoreactive insulin (IRI), thyroxine binding globulin (TBG) and glycemia in 21 obese subjects (5 males, 16 females) grouped according to the average starting blood glucose concentration in: group I, diabetic obese subjects (9 patients); group II, non diabetic obese subjects (12 patients). All patients had no history of recent weight loss due to dietetic therapy or drugs. Blood samples were drawn in the morning at 0, 2, 4, 6, 8 days after total caloric deprivation and 2 days after refeeding. A superimposable variation of weight and glucose concentration were seen in both groups. In addition, no difference was observed in ketone body excretion, SH, TBG, T4, free T4. In group II a significant decrease of IRI was observed during diet (p less than 0.05); T3 decreased (p less than 0.01) and rT3 increased (p less than 0.01) significantly. No variations in T3 and rT3 values were observed in group I. These results are consistent with a possible role of glucose metabolism in the genesis of the low T3 syndrome.

Thyroid-stimulating-hormone (TSH) secretion was studied in 28 normal subjects (12 males; 16 females) and in 8 subjects with prolactin (PRL) secreting tumors (1 male; 7 females) after nomifensine (NOM) administration (200 mg orally). NOM is a drug which activates dopaminergic (DA) neurotransmission at the central nervous system level. Blood samples were drawn every hour for 4 h after NOM or placebo administration. On the 4th h thyrotrophin-releasing-hormone (TRH) was administered in bolus (200 micrograms i.v.), to both groups, and additional samples were collected at 10-, 20-, 30-, 60- and 90-min intervals. The results indicate that in normal subjects, but not in prolactinomas, NOM induces a moderate but significant reduction in TDH secretion. Furthermore, the TSH response to TRH was found to be significantly reduced. No variation was discerned, however, in PRL secretion after NOM. The hormone response to TRH remained unaffected. The data confirm that in normal subjects the DA neurotransmission exerts an inhibitory role upon TSH secretion. In subjects affected by prolactinomas, an alteration in central DA availability may be hypothesized.

The Thyroid-stimulating-hormone (TSH) secretion has been studied in 12 normal euthyroid subjects (4 males, 8 females) after nomifensine (NOM) administration (200 mg po). NOM is a drug which activates dopaminergic neurotransmission at the Central Nervous System level. Blood samples were drawn every h for 4 h after NOM or placebo, respectively. At the 4th hour thyrotropin-releasing-hormone (TRH) was administered in bolus (200 micrograms iv), in both studies, and additional samples were collected for 90 min. The results show a moderate suppression (NS) of TSH and a clear-cut reduction in the secretory response to TRH after NOM administration (secretory area: TRH after placebo 723 +/- 132, TRH after NOM 400 +/- 83; p less than 0.01). The data appear to confirm that dopaminergic neurotransmission exerts an inhibitory role upon TSH secretion. The mechanism by which NOM induced dopaminergic activation leads to the suppression of TSH release after TRH has not yet been elucidated. An interference in TSH storage and/or in the post receptor mechanisms involved in TRH action might be hypothesized.