Male-female differences in 6-sulfatoxymelatonin excretion in hypopituitary patients

ABSTRACT Objective To evaluate melatonin secretion in adult hypopituitary patients with Growth Hormone deficiency (AGHD) on and off replacement therapy. Subjects and methods We studied 48 subjects: 12 (6 males) untreated AGHD (AGHDnt), 20 (10 males) treated AGHD (AGHDt) and 16 healthy subjects (8 males) as control group (CG). We measured urinary 6-sulfatoxymelatonin (6-SM) in total (24 h samples), nocturnal (6-SMn): 1800-0800 and diurnal samples (6-SMd): 0800-1800. Results Significant differences were observed among the 3 groups of male subjects, in total 6-SM (p < 0.05), nocturnal 6-SM (p < 0.02) and nighttime-daytime delta values (p < 0.003). CG had significantly higher values than the AGHDnt in total 6-SM (p < 0.01), nocturnal 6-SM (p < 0.05) and nighttime-daytime delta values (p < 0.01). AGHDt patients showed significantly higher levels in nighttime-daytime delta values than AGHDnt patients (p < 0.05). In females, no significant differences were found among the 3 groups studied in total, nocturnal, diurnal or nighttime-daytime delta values. In males, significant correlations were found among total 6-SM (r = 0.58; p = 0.029), nocturnal 6-SM (r = 0.70; p = 0.006) and nighttime-daytime delta values (r = 0.71; p = 0.004) vs. serum IGF-1 levels in subjects evaluated. In females, significant correlations were found among total 6-SM (r = 0.57; p = 0.02) vs. serum IGF-1 levels in subjects evaluated. A tendency towards a significant correlation was found in diurnal 6-SM (r = 0.48; p = 0.07). Conclusions Our findings show a sexual dimorphism in 6-SM excretion in AGHD patients and provide an interesting approach to a further understanding of some chronobiological disorders involved in GH deficiency.

Burden of Growth Hormone Deficiency and Excess in Children.

Longitudinal growth results from multifactorial and complex processes that take place in the context of different genetic traits and environmental influences. Thus, in view of the difficulties in comprehension of the physiological mechanisms involved in the achievement of normal height, our ability to make a definitive diagnosis of GH impairment still remains limited. There is a myriad of controversial aspects in relation to GH deficiency, mainly related to diagnostic controversies and advances in molecular biology. This might explain the diversity in therapeutic responses and may also serve as a rationale for new "nonclassical" treatment indications for GH. It is necessary to acquire more effective tools to reach an adequate evaluation, particularly while considering the long-term implications of a correct diagnosis, the cost, and safety of treatments. On the other hand, overgrowth constitutes a heterogeneous group of different pathophysiological situations including excessive somatic and visceral growth. There are overlaps in clinical and molecular features among overgrowth syndromes, which constitute the real burden for an accurate diagnosis. In conclusion, both GH deficiency and overgrowth are a great dilemma, still not completely solved. In this chapter, we review the most burdensome aspects related to short stature, GH deficiency, and excess in children, avoiding any details about well-known issues that have been extensively discussed in the literature.

Male-female differences in 6-sulfatoxymelatonin excretion in hypopituitary patients.

OBJECTIVE: To evaluate melatonin secretion in adult hypopituitary patients with Growth Hormone deficiency (AGHD) on and off replacement therapy. SUBJECTS AND METHODS: We studied 48 subjects: 12 (6 males) untreated AGHD (AGHDnt), 20 (10 males) treated AGHD (AGHDt) and 16 healthy subjects (8 males) as control group (CG). We measured urinary 6-sulfatoxymelatonin (6-SM) in total (24 h samples), nocturnal (6-SMn): 1800-0800 and diurnal samples (6-SMd): 0800-1800. RESULTS: Significant differences were observed among the 3 groups of male subjects, in total 6-SM (p < 0.05), nocturnal 6-SM (p < 0.02) and nighttime-daytime delta values (p < 0.003). CG had significantly higher values than the AGHDnt in total 6-SM (p < 0.01), nocturnal 6-SM (p < 0.05) and nighttime-daytime delta values (p < 0.01). AGHDt patients showed significantly higher levels in nighttime-daytime delta values than AGHDnt patients (p < 0.05). In females, no significant differences were found among the 3 groups studied in total, nocturnal, diurnal or nighttime-daytime delta values. In males, significant correlations were found among total 6-SM (r = 0.58; p = 0.029), nocturnal 6-SM (r = 0.70; p = 0.006) and nighttime-daytime delta values (r = 0.71; p = 0.004) vs. serum IGF-1 levels in subjects evaluated. In females, significant correlations were found among total 6-SM (r = 0.57; p = 0.02) vs. serum IGF-1 levels in subjects evaluated. A tendency towards a significant correlation was found in diurnal 6-SM (r = 0.48; p = 0.07). CONCLUSIONS: Our findings show a sexual dimorphism in 6-SM excretion in AGHD patients and provide an interesting approach to a further understanding of some chronobiological disorders involved in GH deficiency.

Decreased 6-Sulfatoxymelatonin Excretion in Male GH-Deficient Children and Adolescents.

AIM: To evaluate melatonin secretion in a group of untreated and treated male growth hormone (GH)-deficient children and adolescents. METHODS: We studied 44 male subjects: 8 untreated GH-deficient patients (GHDnt), 16 treated GH-deficient patients (GHDt) and 20 healthy children and adolescents as control group (CG). We measured urinary 6-sulfatoxymelatonin (6-SM) in total (24-hour samples), nocturnal (18.00-8.00 h) and diurnal samples (8.00-18.00 h). Levels of 6-SM were expressed as micrograms excreted per time interval and x0394; values (difference between nighttime and daytime values). RESULTS: Significant differences were observed among the 3 groups of pediatric subjects studied for total 6-SM (p < 0.0001), nocturnal 6-SM (p < 0.0001) and x0394; values (p < 0.0001). Subsequent analysis showed significantly higher levels for total 6-SM, nocturnal 6-SM and nighttime-daytime x0394; in the CG versus the GHDnt (p < 0.01) and in the CG versus the GHDt group (p < 0.01). No significant correlations were found between 6-SM excretion and insulin-like growth factor-1 values in the children and adolescents studied. CONCLUSIONS: GH-deficient patients showed lower levels of 6-SM. Our findings provide a different insight to a further understanding of some chronobiological disorders involved in GH deficiency in children.

Promoting excellence in the care of pediatric endocrine diseases in the developing world.

On behalf of the Global Pediatric Endocrinology and Diabetes group, the authors provide a perspective on the rights of a child as enshrined in the United Nations Convention on the Rights of the Child (1989) concerning the care of pediatric endocrine disorders and diabetes mellitus, throughout the world, with particular reference to care in resource-constrained settings. In this article, we define the spectrum of health care needs of the child with an endocrine disorder and how they may be addressed, in terms of education, research, and development of sustainable programs for improved health outcomes. We emphasize the responsibilities of medical communities, the pharmaceutical industry, and relevant governments in promoting and supporting such concepts.

GH deficiency during the transition period: clinical characteristics before and after GH replacement therapy in two different subgroups of patients.

OBJECTIVE: To study two subsets of patients with GH deficiency (GHD) during the transition period: childhood onset GHD (CO-GHD) and patients who develop GHD during the transition phase (TO-GHD) before and after GH replacement. PATIENTS AND MEASUREMENTS: In 1340 GHD subjects from KIMS (Pfizer International Metabolic Database), CO (n=586) or TO (n=754), background characteristics, anthropometric measurements, IGF-1, lipids and quality of life (QoL) were evaluated at baseline and after 3 years of GH replacement. RESULTS: Both groups responded similarly to GH treatment. Changes of clinical outcomes were mainly determined by their value at baseline. Onset of the disease in childhood or transition period did not appear to be a significant predictor of response in any of the clinical outcomes. CONCLUSIONS: Age at GHD diagnosis was a significant predictor for many outcomes at baseline, but disease onset did not appear as an independent predictor concerning changes after 3 years of GH treatment. The results suggest that GH replacement during the transition period should be considered independently of the onset of the deficiency.

Confirmation of neonatal screening: reference intervals and evaluation of methodological changes in TSH measurement.

Neonatal reference values for serum thyrotropin are scarce and comprise only small numbers of patients. During 2006, changes were made in IMMULITE kits for TSH measurement. To validate methodological changes, 80 serum samples from patients were evaluated and to establish reference intervals, 334 neonates and infants were analyzed (divided into 4 groups). Group 1 (G1) (48-72 h of life) (n=153), group 2A (G2A) (7-10 days of life) (n=65), group 2B (G2B) (11-14 days of life) (n=35), group 3 (G3) (28-40 days of life) (n=81). Current kits overestimate TSH results by 26 to 37%; TSH (mIU/L) reference intervals (percentile 2.5-97.5) were G1 (1.1-12.7), G2A (1.8-9.8), G2B (1.1-7.1) (p < 0.03 vs. G2A), G3 (1.2-6.9). We suggest that during the second week of life, reference values should be divided into an early stage and a late stage, at least, for there to be an adequate interpretation of borderline measurements in newborn thyroid screening.

Medium and long-term outcome of growth hormone therapy in growth hormone deficient adults.

We evaluated long-term replacement therapy outcomes in various subsets of patients with adult growth hormone (GH) deficiency (AGHD) as well as the patients' susceptibility to adverse events. Fifty-nine patients with AGHD were evaluated, 27 with childhood onset (CO) (18-44 years old, 12 females) and 32 with adult onset (AO) (27-70 years, 18 females). A significant improvement in HDL-cholesterol was observed in AGHD-AO males (basal: 41.3 +/- 12.9 mg/dl, intratreatment: 47.5 +/- 13.2 mg/dl, p = 0.009). However, individual analyses showed that total cholesterol decreased below 240 mg/dl in 33% of AGHD-CO patients and in 50% of AGHD-AO patients, and below 200 mg/dl in 67% of AGHD-CO patients and in 29% of AGHD-AO patients; in the AGHD-AO group, normalization of LDL-cholesterol (< or = 160 mg/dl) and triglycerides (< or = 200 mg/dl) was found in 100% and 50% of patients, respectively; the total cholesterol/HDL ratio decreased below 4.5 in 20% of AGHD-CO patients and in 25% of AGHD-AO patients. The cardiological evaluation showed a significant intra- and interindividual heterogeneity, but cardiac mass improved in patients with a baseline cardiac mass index below 60 g/m2. Markers of bone apposition increased significantly, while bone resorption markers were found to remain unchanged during treatment. A correlation was found between increased bone mineral content and lean body mass (p = 0.0009). Susceptibility to adverse events was not found to be dependent on gender or on the time of onset of the deficiency. Our findings would appear to confirm that a more severe metabolic impairment is correlated with a better therapeutic outcome.

Gender-related differences in urinary 6-sulfatoxymelatonin levels in obese pubertal individuals.

The objective of this study was to measure the urinary excretion of the main melatonin metabolite 6-sulfatoxymelatonin in obese and normal weight (wt) boys and girls. The study included 94 subjects, aged 4-15.7 yr (50 obese and 44 normal wt; 48 boys) classified as: mid-childhood (4-7.99 yr), late-childhood (8-12 yr) and pubertal (10.1-15.7 yr, Tanner II-IV). Normal wt subjects were children with a body mass index (BMI) between the 25th and 75th percentiles, and the group of obese subjects included children whose BMI was above the 97th percentile. A 24-hr urine sample was collected during two intervals: (i) 18:00-08:00 hr, and (ii) 08:00-18:00 hr. Analysis of urinary 6-sulfatoxymelatonin levels was performed by radioimmunoassay. Excretion of 6-sulfatoxymelatonin was expressed as: (i) total amount excreted (microg); (ii) mug excreted per time interval, nocturnal or diurnal; and (iii) the difference between nocturnal and diurnal samples (microg, estimated amplitude). A factorial analysis of variance indicated that nocturnal 6-sulfatoxymelatonin excretion and amplitude were significantly higher in the obese individuals. A significant interaction 'BMI x age' was detected, i.e. the effect of BMI was significant in the pubertal group only. Total, nocturnal and diurnal 6-sulfatoxymelatonin excretion was significantly higher in girls. The increase in 6-sulfatoxymelatonin excretion found in obesity occurred only in boys and at the pubertal age. To what extent this increase in melatonin production contributes to a delayed puberty in some pubertal obese males remains to be established.

Adult growth hormone deficiency. Metabolic alterations and evaluation of different risk groups.

Adult growth hormone deficiency (AGHD) is an heterogeneous clinical entity characterized by increased cardiovascular morbidity and mortality, alterations in body composition, osteoporosis and impaired quality of life. In order to characterize higher risk subpopulations we studied 77 patients with AGHD, 35 with childhood onset (AGHD-CO): CA 18-44 yr.; 13 females and 22 males, and 42 with adult onset (AGHD-AO): CA 25-70 yr.; 22 females and 20 males. IGF-I, lipid profile, glycemia and glycosylated hemoglobin were measured. Cardiological evaluation: blood pressure, electrocardiogram, ergometry and 2D echocardiogram with mitral Doppler, evaluation of diastolic function (A/E waves ratio and deceleration time), systolic function (ejection and shortening fractions) and Cardiac Mass Index (CMI). The Body Mass Index and waist circumference were recorded. Total body composition and bone mineral density were evaluated by densitometry, and the following bone markers were measured: osteocalcin, bone-specific alkaline phosphatase, carboxyterminal propeptide of type I procollagen, Pyridinoline and Deoxipyridinoline. The subset of females with AGHD-AO had higher levels of total cholesterol: 240 mg/dl (156-351) (p < 0.005), LDL: 140 mg/dl (62-262) (p < 0.04) and of total cholesterol/HDL: 4.04 (3.12-12.7) (p < 0.04); while females with AGHD-CO had a decreased CMI: 62 g/m2 (53-107) (p < 0.01), lower A/E waves ratio: 0.56 (0.39-0.72) (p < 0.01) and lower deceleration time: 164 msec. (135-210) (p < 0.01). The subset of males with AGHD-AO had a greater waist circumference: 98 cm (83-128) (p < 0.03) and males with AGHD-CO had a lower shortening fraction: 41% (30-49) (p < 0.006) and lower deceleration time: 153.5 msec. (127-230) (p < 0.03). In both genders, the bone mineral content was lower in patients with AGHD-CO (females p < 0.02, males: p < 0.0008). Our findings confirm the differences in impairment in AGHD patients, which are mainly dependent on gender and the time of onset of the deficiency, and thus demonstrate the heterogeneity of the syndrome.

Adult growth hormone deficiency metabolic alterations and evaluation of different risk groups

El déficit de hormona de crecimiento (GH) del Adulto (AGHD) es una entidad clínica heterogénea caracterizada por incremento de la morbimortalidad cardiovascular, cambios en la composición corporal, osteoporosis y deterioro de la calidad de vida. Para caracterizar subpoblaciones con mayor riesgo de afectación, estudiamos 77 pacientes AGHD, 35 de inicio en la infancia (AGHD-CO): EC 18-44 a; 13 mujeres y 22 varones, y 42 de inicio en la adultez (AGHD-AO): EC 25-70 a; 22 mujeres y 20 varones. Se midió IGF-I, perfil lipídico, glucemia y hemoglobina glicosilada. Evaluación cardiológica: tensión arterial, electrocardiograma, ergometría y ecocardiograma bidimensional con Doppler mitral, evaluando función diastólica (relación ondas A/E y tiempo de desaceleración), función sistólica (fracciones de eyección y acortamiento) e índice de masa cardíaca (IMC). Se registró el índice de masa corporal y la circunferencia de cintura. Se evaluó, mediante densitometría, la composición corporal total y la densidad mineral ósea y se dosaron marcadores óseos: osteocalcina, fosfatasa alcalina fracción ósea, propéptido tipo I carboxiterminal del procolágeno, Pyridinolina y Deoxipyridinolina. El subgrupo de mujeres AGHD-AO presentó mayores niveles de colesterol total: 240 mg/dl (156-351) (p< 0.005), LDL: 140 mg/dl (62-262) (p< 0.04) y de colesterol total / HDL: 4.04 (3.12-12.7) (p< 0.04); mientras que las mujeres AGHD-CO presentaron menor IMC: 62 g/m2 (53-107) (p< 0.01), menor relación A/E: 0.56 (0.39-0.72) (p< 0.01) y menor tiempo de desaceleración: 164 mseg (135-210) (p< 0.01). El subgrupo de varones AGHD-AO presentó mayor circunferencia de cintura: 98 cm (83-128) (p< 0.03) y los varones AGHD-CO, menor fracción de acortamiento: 41% (30-49) (p< 0.006) y menor tiempo de desaceleración: 153.5 mseg (127-230) (p< 0.03). En ambos sexos, el contenido mineral óseo fue menor en los pacientes AGHD-CO (mujeres p< 0.02, varones: p< 0.0008). Nuestros hallazgos confirman la diferente afectación de los pacientes AGHD, en particular en relación al sexo y al momento de inicio de la deficiencia, demostrando la heterogeneidad del síndrome.

Adult growth hormone deficiency. Metabolic alterations and evaluation of different risk groups.

Adult growth hormone deficiency (AGHD) is an heterogeneous clinical entity characterized by increased cardiovascular morbidity and mortality, alterations in body composition, osteoporosis and impaired quality of life. In order to characterize higher risk subpopulations we studied 77 patients with AGHD, 35 with childhood onset (AGHD-CO): CA 18-44 yr.; 13 females and 22 males, and 42 with adult onset (AGHD-AO): CA 25-70 yr.; 22 females and 20 males. IGF-I, lipid profile, glycemia and glycosylated hemoglobin were measured. Cardiological evaluation: blood pressure, electrocardiogram, ergometry and 2D echocardiogram with mitral Doppler, evaluation of diastolic function (A/E waves ratio and deceleration time), systolic function (ejection and shortening fractions) and Cardiac Mass Index (CMI). The Body Mass Index and waist circumference were recorded. Total body composition and bone mineral density were evaluated by densitometry, and the following bone markers were measured: osteocalcin, bone-specific alkaline phosphatase, carboxyterminal propeptide of type I procollagen, Pyridinoline and Deoxipyridinoline. The subset of females with AGHD-AO had higher levels of total cholesterol: 240 mg/dl (156-351) (p < 0.005), LDL: 140 mg/dl (62-262) (p < 0.04) and of total cholesterol/HDL: 4.04 (3.12-12.7) (p < 0.04); while females with AGHD-CO had a decreased CMI: 62 g/m2 (53-107) (p < 0.01), lower A/E waves ratio: 0.56 (0.39-0.72) (p < 0.01) and lower deceleration time: 164 msec. (135-210) (p < 0.01). The subset of males with AGHD-AO had a greater waist circumference: 98 cm (83-128) (p < 0.03) and males with AGHD-CO had a lower shortening fraction: 41

(30-49) (p < 0.006) and lower deceleration time: 153.5 msec. (127-230) (p < 0.03). In both genders, the bone mineral content was lower in patients with AGHD-CO (females p < 0.02, males: p < 0.0008). Our findings confirm the differences in impairment in AGHD patients, which are mainly dependent on gender and the time of onset of the deficiency, and thus demonstrate the heterogeneity of the syndrome.

Adult growth hormone deficiency metabolic alterations and evaluation of different risk groups

El déficit de hormona de crecimiento (GH) del Adulto (AGHD) es una entidad clínica heterogénea caracterizada por incremento de la morbimortalidad cardiovascular, cambios en la composición corporal, osteoporosis y deterioro de la calidad de vida. Para caracterizar subpoblaciones con mayor riesgo de afectación, estudiamos 77 pacientes AGHD, 35 de inicio en la infancia (AGHD-CO): EC 18-44 a; 13 mujeres y 22 varones, y 42 de inicio en la adultez (AGHD-AO): EC 25-70 a; 22 mujeres y 20 varones. Se midió IGF-I, perfil lipídico, glucemia y hemoglobina glicosilada. Evaluación cardiológica: tensión arterial, electrocardiograma, ergometría y ecocardiograma bidimensional con Doppler mitral, evaluando función diastólica (relación ondas A/E y tiempo de desaceleración), función sistólica (fracciones de eyección y acortamiento) e índice de masa cardíaca (IMC). Se registró el índice de masa corporal y la circunferencia de cintura. Se evaluó, mediante densitometría, la composición corporal total y la densidad mineral ósea y se dosaron marcadores óseos: osteocalcina, fosfatasa alcalina fracción ósea, propéptido tipo I carboxiterminal del procolágeno, Pyridinolina y Deoxipyridinolina. El subgrupo de mujeres AGHD-AO presentó mayores niveles de colesterol total: 240 mg/dl (156-351) (p< 0.005), LDL: 140 mg/dl (62-262) (p< 0.04) y de colesterol total / HDL: 4.04 (3.12-12.7) (p< 0.04); mientras que las mujeres AGHD-CO presentaron menor IMC: 62 g/m2 (53-107) (p< 0.01), menor relación A/E: 0.56 (0.39-0.72) (p< 0.01) y menor tiempo de desaceleración: 164 mseg (135-210) (p< 0.01). El subgrupo de varones AGHD-AO presentó mayor circunferencia de cintura: 98 cm (83-128) (p< 0.03) y los varones AGHD-CO, menor fracción de acortamiento: 41% (30-49) (p< 0.006) y menor tiempo de desaceleración: 153.5 mseg (127-230) (p< 0.03). En ambos sexos, el contenido mineral óseo fue menor en los pacientes AGHD-CO (mujeres p< 0.02, varones: p< 0.0008). Nuestros hallazgos confirman la diferente afectación de los pacientes AGHD, en particular en relación al sexo y al momento de inicio de la deficiencia, demostrando la heterogeneidad del síndrome.(AU)

Evaluation of diagnostic accuracy of insulin-like growth factor (IGF)-I and IGF-binding protein-3 in growth hormone-deficient children and adults using ROC plot analysis.

We critically evaluated the diagnostic value of IGF-I and IGF-binding protein-3 (IGFBP-3) in GH deficiency (GHD) in children and adults using receiver operating characteristic (ROC) plot analysis. Sixty-six children (chronological age, 1.3-15 yr) were studied: 34 GHD and 32 idiopathic short stature (ISS). Ninety-two adults (chronological age, 18-70 yr) were also evaluated: 72 GHD, 34 of childhood onset (AGHD-CO), and 38 of adult onset (AGHD-AO); and 20 healthy volunteers. The SD score (SDS) for IGF-I was calculated from 596 normal subjects (212 children and 384 adults), and the SDS for IGFBP-3 was calculated from 350 normal subjects (212 children and 138 adults). The ROC plot showed that the best IGF-I SDS cut-off line was -1.65 for children [sensitivity (S), 68%; specificity (Sp), 97%, diagnostic efficiency (DEf), 81%], the cut-off line for AGHD was -1.65 for AGHD-CO (S, 91%; Sp, 100%; DEf, 94%), and the cut-off line for AGHD-AO was -1.80 (S, 81%; Sp, 100%; DEf, 88%). For IGFBP-3 SDS, the best cut-off line was -1.80 for children (S, 90%; Sp, 60%; DEf, 78%); it was -1.45 for AGHD-CO (S, 90%; Sp, 75%; DEf, 82%) and -0.90 for AGHD-AO (S, 90%; Sp, 68%; DEf, 77%). An accurate diagnosis was obtained using IGF-I SDS alone in GHD children 65%; ISS, 97%; AGHD-CO, 92%; AGHD-AO, 86%, with IGFBP-3 SDS alone in GHD children 60%; ISS, 90%; AGHD-CO, 75%; AGHD-AO, 68%. Considering both, an accurate diagnosis was obtained in GHD children 60%; ISS, 87%; AGHD-CO, 71%; AGHD-AO, 64%. In conclusion, our findings support the need to use cut-off lines expressed in SDS obtained using an appropriate statistical methodology for better characterization of the various clinical presentations. IGF-I proved to be more useful because of its good diagnostic efficiency and accuracy in both children and adults, whereas IGFBP-3 did not significantly contribute to the diagnosis of GHD.

Tumoral versus non-tumoral hyperprolactinemia in children and adolescents: possible usefulness of the domperidone test.

UNLABELLED: The aim of this study was to evaluate the usefulness of the domperidone test for the difficult diagnosis between functional and tumoral hyperprolactinemia. We evaluated 36 patients, aged 5-18 years, 14 (12 F, 2 M) with hyperprolactinemia (non-tumoral: 10; pituitary adenoma: 4) and 22 individuals as a control group (prepubertal: 5 F, 8 M; pubertal: 4 F, 5 M). Basal prolactin (PRL) (IRMA-DPC), T4 and TSH and PRL 30 min post-domperidone (0.2 mg/kg b. wt i.v.) were measured. Non-tumoral hyperprolactinemic females showed basal PRL: 45 (29-80) (median and range) ng/ml; post-domperidone: 208 (116-290) ng/ml; delta PRL (PRL 30' - PRL 0'): 167 (77-252) ng/ml; and PRL ratio (PRL 30'/PRL 0'): 3.9 (2.3-7.6). Females with pituitary adenoma showed basal PRL: 129 (125-660) ng/ml; post-domperidone: 202 (150-535) ng/ml; delta PRL: 73 (25-135) ng/ml; and ratio: 1.2 (0.8-1.6). Two males, one with a non-tumoral hyperprolactinemia and the other one with a pituitary adenoma, presented, respectively, PRL 0':45, 160; PRL 30':130, 173; delta: 85, 13; ratio: 2.9, 1.1. All non-tumoral patients showed a PRL ratio (30'/0') > 2.3, while no patient with pituitary adenoma had a ratio > 1.6. CONCLUSIONS: PRL response to domperidone allowed us to characterize hyperprolactinemias, although the presence of a blunted response should be confirmed in a larger number of patients with tumors with 'low' PRL levels (dependence on etiology or basal PRL level?).