Clinical use of pre- and postsurgical evaluation of abnormal GH responses in acromegaly

Abstract

The criteria by which acromegalic patients are considered "cured" after surgical therapy are still controversial. Since the abnormal growth hormone (GH) increase after the administration of some agents has been demonstrated to be characteristic of the tumoral somatotrophs, its disappearance after surgery may be taken as an index of the complete removal of the tumor. Serum GH increases after thyrotropin-releasing hormone (TRH, 200 micrograms intravenously), gonadotropin-releasing hormone (Gn-RH, 100 micrograms intravenously), and sulpiride (100 mg intramuscularly) injected during dopamine infusion (DA-Slp test), were evaluated in 68 acromegalic patients before and after transnasosphenoidal adenomectomy, and every 12 to 18 months during a follow-up period of 6 months to 11 years (average 42 months). Forty-two patients had abnormal responses to at least one test before surgery: 32 out of 68 (47%) to TRH, six out of 40 (15%) to Gn-RH, and 20 out of 28 (71%) to the DA-Slp test. Of 18 patients who underwent all three tests, 78% had abnormal responses to at least one of them. Twenty-three patients became unresponsive after surgery, and none of them had a recurrence or became abnormally responsive again during the follow-up period. Three out of six patients with postoperative serum GH levels between 5.1 and 10 ng/ml and three out of six patients with postoperative serum GH levels between 2.1 and 5 ng/ml remained abnormally responsive: one of them relapsed 1 year after the operation. The abnormal responses were lost in all 11 patients whose postoperative serum GH levels were below 2 ng/ml, and abnormal responses were maintained in all the patients in whom surgery was considered unsuccessful because postoperative serum GH levels were higher than 10 ng/ml. The TRH, Gn-RH, and DA-Slp tests should thus be considered useful tools in verifying the total removal of an adenoma. The reappearance of active acromegaly in the patient with low postoperative GH levels, who was still responsive to TRH, should be regarded as a reactivation and not a true recurrence of the disease.

Preoperative growth hormone response to thyrotropin-releasing hormone and oral glucose tolerance test in acromegaly: A retrospective evaluation of 50 patients

“…Normal urinary free cortisol ranges from 20 to 90 g/24 h. As previously suggested, a positive GH response to TRH was defined as a serum GH increase greater than 50% of basal values. 18 Partial GH inhibition after OGTT was defined, according to data in the literature, 14,19 as a GH nadir at least 30% below basal levels. These definitions allow us to distinguish a GH response from spontaneous changes in the GH secretion.…”

“…These definitions allow us to distinguish a GH response from spontaneous changes in the GH secretion. 14,18,19 Concerning the postoperative results, we considered "controlled" the patients who presented undetectable GH (Ͻ1 g/L) in the course of a glucose tolerance test, IGF-I plasma values in the normal range, matched for age and sex, no clinical activity, 15 and no neuroradiologic recurrence (CT scan and MRI, respectively, in 28 and in 22 patients) after a 5-year follow-up. We considered "poorly controlled" those patients who still showed elevated GH and IGF-I plasma levels, uninhibited GH (Ͼ1 g/L) after a glucose tolerance test, and clinical activity 15 and/or radiologic signs of adenoma recurrence, even if a reduction of tumour size had been demonstrated.…”

Diagnostic Value of the Acid-Labile Subunit in Acromegaly: Evaluation in Comparison with Insulin-Like Growth Factor (IGF) I, and IGF-Binding Protein-1, -2, and -3

“…One patient presenting with IGF-I level above the 97th percentile of the control group and nadir GH after OGTT below 1 g/L was considered to have persistent disease. Two other patients, in whom GH decreased to 1 g/L and not less than 1 after OGTT while abnormal GH responses were maintained, were not considered cured (27). Gonadal function normalized in 3 men and worsened in 2; all other anterior pituitary functions were unchanged.…”

Neurosurgery restores late GH rise after glucose-induced suppression in cured acromegalics

“…Other criteria to evaluate cure of acromegalic patients include the disappearance of paradoxical stimuli for GH secretion, such as thyrotropin-releasing hormone (TRH) (2), and the restoration of normal GH dynamics (3).…”