GH sensitivity of GH-deficient adults is dependent on gender but not timing of onset.

BACKGROUND: Females secrete 2-3 -fold greater amounts of GH compared with males despite maintaining similar IGF-I levels. IGF-I generation tests in healthy subjects suggest this discordancy results from relative resistance to GH in females. In GHD females the presumed relative insensitivity to GH is reflected by a lower basal IGF-I and the need for higher GH maintenance doses during replacement. Adults with severe GHD of childhood-onset (CO) have lower basal IGF-I SDS and require higher GH maintenance doses compared with adult-onset (AO) patients with GHD of equal severity. We hypothesised CO-GHD adults to be less sensitive to GH than AO-GHD patients. METHODOLOGY: In a single site study we analysed the incremental change in IGF-I (DeltaIGF-I) in 116 GHD adults following initiation of GH replacement. The data were corrected to provide DeltaIGF-I/mg GH because of slight variances in initial GH dose. RESULTS: Following GH replacement DeltaIGF-I was 230 +/- 245 and 356 +/- 278 ng/ml/mg GH in females and males, respectively (P = 0.01). In CO and AO patients DeltaIGF-I was 282 +/- 206 and 294 +/- 292 ng/ml/mg GH, respectively (P = 0.83). Further analysis after stratification by both gender and timing of onset of GHD showed DeltaIGF-I was 226 +/- 164, 324 +/- 228, 231 +/- 268, and 373 +/- 304 ng/ml/mg GH in the CO females, CO males, AO females, and AO males, respectively (AO males vs. AO females, P = 0.03; CO males vs. CO females, P = 0.17; AO males vs. CO males, P > 0.05; AO females vs. CO females, P > 0.05). Multiple linear regression with DeltaIGF-I as the dependent variable and age, gender, BMI, baseline IGF-I level, and timing of onset as independent variables showed DeltaIGF-I to be dependent on gender alone (R = 0.28, P = 0.004). Age (P = 0.44), BMI (P = 0.54), baseline IGF-I level (P = 0.63) and timing of onset (P = 0.61) had no effect on DeltaIGF-I. CONCLUSION: We have shown gender to have a significant impact on GH sensitivity in GHD adults, which, at least in part, explains differences in maintenance dosages during replacement. None of the additional variables impacted significantly on GH sensitivity. The lower basal IGF-I SDS and higher GH replacement requirement reported in CO compared with AO patients cannot be explained by differences in sensitivity to GH.

Low bone mass is an infrequent feature of the adult growth hormone deficiency syndrome in middle-age adults and the elderly.

Low bone mass is considered a characteristic feature of adult GH deficiency (GHD). Although low bone mass is universally observed in cohorts of GHD adults of young age, the situation is less clear with regard to cohorts of GHD middle-age adults or the elderly. We have examined the relationship between bone mineral density (BMD) and age in 125 severely GHD adults using dual-energy x-ray absorptiometry. This relationship was further examined with a calculated measure of volumetric BMD, bone mineral apparent density (BMAD). A significant positive correlation was observed between age and BMD (Z scores) at the lumbar spine (r = 0.39, P < 0.0001), femoral neck (r = 0.47, P < 0.0001), total hip (r = 0.47, P < 0.0001), and ultradistal (r = 0.46, P < 0.0001) and distal radius (r = 0.52, P < 0.0001). Young adults were observed to have reduced bone mass, whereas the elderly GHD patients had normal Z scores. After division of the cohort into age ranges (<30, 30-45, 45-60, and >60 yr), BMD Z scores at all five skeletal sites increased significantly across the age groups from youngest to oldest (P < 0.001). When BMD was assessed using absolute values (g/cm(2)), in contrast to the decline in BMD observed with aging in a normal population, BMD at the total hip and ultradistal and distal radius increased across the age strata of GHD adults (P = 0.003, P = 0.004, and P = 0.002, respectively), and a trend toward an increase in lumbar spine and femoral neck BMD was also observed. No significant change in BMAD was observed across the four age groups. The percentage of patients observed to have BMD Z scores of less than -2.0 at the lumbar spine was 30, 11, 11, and 14% in the four age groups, respectively. At the femoral neck, the corresponding percentages were 36, 6, 7, and 0%, respectively. In summary, we have shown that the effect of severe GHD on BMD is dependent on age. Low bone mass was observed in the young patients; however, patients over the age of 60 yr demonstrated a mean BMD Z score above that of the reference population and significantly greater BMD (g/cm(2)) when compared with young GHD adults. Few patients were observed to have BMD Z scores below -2.0 except patients aged less than 30 yr, which, in part, was explained by their shorter stature. Thus, significantly reduced bone mass is not a frequent observation in adults with GHD.

Acquired prolactin deficiency indicates severe hypopituitarism in patients with disease of the hypothalamic-pituitary axis.

OBJECTIVE: Prolactin deficiency has been the subject of many scientific studies, but there is a paucity of information regarding prolactin deficiency in humans. In this report, adults with disease of the hypothalamic-pituitary axis (HPA) were studied to determine the prevalence of severe acquired prolactin deficiency (APD) and the pathophysiological characteristics associated with it. PATIENTS AND METHODS: APD was defined as a serum prolactin level persistently below the detection limit of the assay, i.e. less than 50 mU/l (normal range: male 85-444, female 85-530). Patients with a diagnosis of acromegaly, prolactinoma or with congenital or drug induced prolactin deficiency were excluded. Three hundred and sixty-nine patients (190 women, age range 17-79 years) with disease of the HPA, meeting the specified criteria were identified. RESULTS: Twenty-two (13 women, age range 29-76 years), showed evidence of APD. Thirteen of the 22 patients with APD had been treated for Cushing's disease. In all, 62 patients treated for Cushing's disease were identified, resulting in a prevalence of APD in treated Cushing's disease of 20.97%. Excluding treated Cushing's disease, the prevalence of APD in the remainder of the cohort was 2.93%. Nineteen patients with APD (86.4%) and 183 without APD (52.7%) underwent surgery in the region of the HPA (P = 0.0042). In contrast, nine patients with APD (40.9%) and 283 without APD (80.4%) had received radiotherapy, with fields which included the HPA (P < 0.001). No patient with isolated APD was identified. All patients with APD had evidence of severe GH deficiency (GHD) with a peak GH response to provocative stimuli of < 1.6 mU/l and a median IGF-I standard deviation score (SDS) of -4.85 (quartiles -9.56 to -2.80). Of the 13 patients with APD and Cushing's disease, all were gonadotrophin and TSH-deficient, six were adrenocorticotropic hormone (ACTH)-deficient and six (46.1%) had cranial diabetes insipidus (CDI). Of the remaining nine patients with APD, total anterior pituitary hormone failure was present in all and CDI was present in two (22.2%). CONCLUSIONS: The presence of APD indicates severe hypopituitarism in adults with HPA disease. It is universally associated with severe GHD. It is more common after surgery to the HP region. It has a low overall prevalence except in patients surgically treated for Cushing's disease.