Effect of gastrointestinal hormones on isolated bovine parathyroid cells.

The effects of gastrointestinal hormones on cAMP accumulation and parathyroid hormone (PTH) release were investigated in dispersed bovine parathyroid cells. Secretin (10 (-7) M) caused a 4- to 6-fold increase in cAMP accumulation, while glucagon, vasoactive intestinal peptide, and gastrin caused little if any stimulation. Cholecystokinin caused a 2- to 3-fold increase in cAMP accumulation at 10(-6) M, but this effect may be related to contamination with endogenous secretin since synthetic cholecystokinin octapeptide had no effect. Maximal intracellular cAMP accumulation due to 10(-7) M secretin was reached within 5 min and returned to control over the next 30-60 min, concomitant with a progressive rise in extracellular cyclic nucleotide. cAMP accumulation was half-maximally stimulated by 5 x 10(-9) to 1 x 10(-8) M secretin and was unaffected by alpha- or beta-adrenergic or dopaminergic blockers. Parallel effects were noted on PTH release : 10(-8) M secretin caused a 20-50% increment in PTH release at 15 min which persisted for up to 2 h; PTH release was stimulated half-maximally by approximately 6--8 x 10(-9) m secretin. The specificity of the observed results for secretin and the lack of effect of adrenergic antagonists suggest the presence of a receptor for secretin on dispersed bovine parathyroid cells. These results also suggest the possibility that secretin may modulate parathyroid function in vivo in the cow.

Failure to respond to growth hormone releasing hormone (GHRH) in acromegaly due to a GHRH secreting pancreatic tumor: dynamics of multiple endocrine testing.

Growth hormone releasing hormone (GHRH) has recently been isolated and sequenced from pancreatic tumors secreting GHRH. Patients with untreated acromegaly due to a pituitary tumor respond to exogenous administration of GHRH with a further rise of their elevated basal growth hormone (GH) levels. For the first time, we report the effects of exogenously administered synthetic GHRH in a patient with acromegaly due to a GHRH secreting pancreatic tumor. The diagnosis was established by high peripheral IR-GHRH levels (1100 pg/ml) and an arterio- venous tumor gradient of IR-GHRH. In this patient GH failed to respond to 1 microgram/kg of exogenous GHRH with the pancreatic tumor in situ; however, further increase of serum GH levels occurred after TRH administration, hypoglycemia and oral glucose administration. After removal of the tumor, serum GH levels decreased and a normal response to GHRH and TRH were demonstrated. The extract of the tumor contained 1.7 micrograms IR-GHRH per g wet tissue. Thus, lack of response to exogenous GHRH in untreated acromegaly may indicate the presence of an ectopic GHRH producing tumor.

Circulating parathyroid hormone activity: familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism.

Three indices of circulating parathyroid hormone (PTH) activity were compared between two groups: the first a group of 23 patients from three large kindreds with autosomal dominant hypercalcemia without hypercalciuria [familial hypocalciuric hypercalcemia (FHH)] and the second a group of 64 patients with typical primary hyperparathyroidism (1HPT) manifesting comparable hypercalcemia. The group with 1HPT differed from normal with respect to plasma PTH 1HPT concentration (normal, less 0.2 ng/ml), urinary cAMP excretion per 100 ml glomerular filtrate (U cAMP/GF) (normal, 2.3 x/divided by 0.6 nmol/100 ml glomerular filtrate; mean, x/divided 1 SD), and renal tubular maximum of phosphate transport corrected for glomerular filtration rate (TMP/GFR; normal, 3.4 +/- 0.4 mg/dl; mean, +/- 1 SD). The group with 1HPT also diverged significantly from the group with FHH for all three indices: for PTH, 0.37 x/divided by .48 vs. 0.25 x/divided .46 (P less than 0.05); for UcAMP/GF, 4.3 x/divided by .53 vs. 2.6 x/divided .60 (P less than 0.0005); and for TMP/GFR, 2.0 +/- 0.6 vs. 2.6 +/- 0.7 (P less than 0.01). The between-group differences for all three indices were also significant after adjustment for their variation with serum calcium. However, only the difference in TMP/GFR remained significant after adjustment for covariance attributable to serum calcium concentration, age, and creatinine clearance. The group with FHH differed from normal for TMP/GFR but not for UcAMP/GF. However, analysis of changes in UcAMP/GF and serum calcium concentration around the time of parathyroidectomy in three patients with FHH suggested that the parathyroid glands contributed to the abnormalities of mineral homeostasis in at least one. It was concluded that higher serum concentrations of PTH do not account for the lower renal clearance of calcium and magnesium in FHH calcium concentration, the group with FHH showed indices suggesting lower circulating PTH activity than the group with 1HPT.

[Localization of an ACTH-producing pituitary microadenoma using bilateral and simultaneous catheterization of the inferior petrosal sinus]. / Lokalisation hypophysärer, ACTH-produzierender Mikroadenome mittels bilateraler und simultaner Katheterisierung des Sinus petrosus inferior.

The experience with bilateral simultaneous inferior petrosal sinus catheterization and determination of the ACTH-concentration in 21 patients is reported. Venous blood sampling in the right and left inferior petrosal sinus was obtained before and after stimulation with Corticotropin-Releasing-Hormone (CRH). In 13 patients with Cushing's Syndrome a ACTH gradient (central versus peripheral) was measured. In all patients who were operated (11/13) a microadenoma was confirmed. In all patients with a central/peripheral gradient of the ACTH-levels at the same time an ipsi versus contralateral gradient between the two sides could be established after administration of CRH, which allowed a correct localization of the microadenoma. In 11 of 13 patients the site of the microadenoma was confirmed intraoperatively.