Search

Purpose: To examine differences in effects according to growth hormone (GH) treatment duration in adult GH-deficient patients., Methods: In the Italian cohort of the observational Hypopituitary Control and Complications Study, GH-treated adults with GH deficiency (GHD) were grouped by duration of treatment; ≤ 2 years (n = 451), > 2 to ≤ 6 years (n = 387) and > 6 years (n = 395). Between-group differences in demographics, medical history, physical characteristics, insulin-like growth factor-I standard deviation score (IGF-I SDS) and lipid profile at baseline, last study visit and changes from baseline to last study visit were assessed overall, for adult- and childhood-onset GHD and by gender using ANOVA for continuous variables and Chi-squared test for categorical variables., Results: At baseline, treatment duration groups did not differ significantly for age, gender, body mass index, GHD onset, IGF-I SDS, lipid profile, and quality of life. Mean initial GH dose did not differ significantly according to treatment duration group in any subgroup, except female patients, with highest mean dose seen in the longest duration group. In the longest duration group for patients overall, adult-onset patients and male patients, there were significant decreases in GH dose from baseline to last visit, and in total and low-density lipoprotein (LDL)-cholesterol concentrations. IGF-I SDS increased, to a greater extent, in the longest duration group for patients overall and female patients., Conclusions: The results show that long-term GH treatment is associated with decreasing GH dose, increased IGF-I, decreased LDL-cholesterol and the presence of surrogate markers that help to give confidence in a diagnosis of GHD.

Context: Antipituitary antibodies (APA) but not antihypothalamus antibodies (AHA) are usually searched for in autoimmune hypopituitarism., Objective: Our objective was to search for AHA and characterize their hypothalamic target in patients with autoimmune hypopituitarism to clarify, on the basis of the cells stained by these antibodies, the occurrence of autoimmune subclinical/clinical central diabetes insipidus (CDI) and/or possible joint hypothalamic contribution to their hypopituitarism., Design: We conducted a cross-sectional cohort study., Patients: Ninety-five APA-positive patients with autoimmune hypopituitarism, 60 without (group 1) and 35 with (group 2) lymphocytic hypophysitis, were studied in comparison with 20 patients with postsurgical hypopituitarism and 50 normal subjects., Main Outcome Measures: AHA by immunofluorescence and posterior pituitary function were evaluated; then AHA-positive sera were retested by double immunofluorescence to identify the hypothalamic cells targeted by AHA., Results: AHA were detected at high titer in 12 patients in group 1 and in eight patients in group 2. They immunostained arginine vasopressin (AVP)-secreting cells in nine of 12 in group 1 and in four of eight in group 2. All AVP cell antibody-positive patients presented with subclinical/clinical CDI; in contrast, four patients with GH/ACTH deficiency but with APA staining only GH-secreting cells showed AHA targeting CRH- secreting cells., Conclusion: The occurrence of CDI in patients with lymphocytic hypophysitis seems due to an autoimmune hypothalamic involvement rather than an expansion of the pituitary inflammatory process. To search for AVP antibody in these patients may help to identify those of them prone to develop an autoimmune CDI. The detection of AHA targeting CRH-secreting cells in some patients with GH/ACTH deficiency but with APA targeting only GH-secreting cells indicates that an autoimmune aggression to hypothalamus is jointly responsible for their hypopituitarism.

Objective: Antipituitary (APA) but not antihypothalamus antibodies (AHA) have been investigated in patients with idiopathic hypopituitarism. This study searched for APA and AHA in some of these patients to investigate whether pituitary or hypothalamic autoimmunity could play a role in their pituitary dysfunction., Design: Sixty-six patients with selective idiopathic hypopituitarism were studied: 27 with ACTH deficiency, 20 with GH deficiency and 19 with hypogonadotropic hypogonadism. Twenty patients with hypopituitarism secondary to hypophysectomy and 50 healthy subjects were enrolled as controls., Measurements: Antipituitary and AHA were evaluated by indirect immunofluorescence in sera of patients and controls. Positive sera were retested by a four-layer double immunofluorescence to identify the cells targeted by these antibodies., Results: Antipituitary were present at high titre in 4 of 27 patients with ACTH deficiency (14·8%), 4 of 20 with GH deficiency (26%) and 5 of 19 with hypogonadotropic hypogonadism (21%) and targeted, respectively, corticotrophs, somatotrophs and gonadotrophs. AHA were found at high titre only in 5 patients with ACTH deficiency (18·5%), mostly targeting corticotrophin-releasing hormone-secreting cells; none of these 5 patients resulted positive for antipituitary antibodies. Among the controls, only 1 hypophysectomized patient resulted APA positive at low titre., Conclusions: Our results suggest that in patients with selective idiopathic hypopituitarism, detection of APA or AHA could better characterize an autoimmune process involving the pituitary or hypothalamus, respectively. In particular, detection of antibodies targeting selectively ACTH-secreting or corticotrophin-releasing hormone-secreting cells may differentiate, respectively secondary from tertiary variants of autoimmune hypoadrenalism., (© 2011 Blackwell Publishing Ltd.)

Stroke is one of the main causes of death and disability in the adult population. Changes in pituitary hormone secretion may be observed during the acute phase of stroke, representing part of the adaptive response to injury. However, reduced pituitary hormone secretion, caused by pituitary and/or hypothalamus damage, may also occur. Hypopituitarism has been observed in 19% of patients with ischemic stroke and 47% of patients with subarachnoid hemorrhage, presenting as an isolated deficiency in most cases. Diabetes insipidus is very rare. Low IGF-I levels, during the acute phase of stroke, have been associated with poor outcome and high mortality. During rehabilitation, higher IGF-I levels have been observed in patients with better outcome, suggesting a neuroprotective role of IGF-I. Accurate evaluation and long-term follow-up of all patients with stroke are necessary to define the prevalence of hypopituitarism, and its relationship with type, severity, and outcome from stroke. Discovery and adequate treatment of possible endocrine deficiencies may improve outcome and quality of life of patients with stroke.

Hypopituitarism represents the consequence of many conditions, in both the adult and child population. It may occur after neurosurgical treatment of brain tumors arising near sella turcica. Much more attention has been focused on lesions far from the hypothalamic-pituitary region as possible causes of pituitary impairment, validating the concept of the particular fragility of these structures. The aim of this study was to evaluate pituitary function in particular GH deficiency (GHD) in patients submitted to neurosurgery for benign tumors of the central nervous system (CNS) not involving hypothalamic-pituitary region. We observed 37 patients with benign brain tumors [13 males, 24 females, age: 54.6+/-13.9 yr; body mass index (BMI): 25.1+/-4.0 kg/m2] performing a basic evaluation of the pituitary function and a dynamic test of the GH/IGF-I axis [GHRH (1 microg/kg iv)+arginine (0.5 g/kg iv) test] for 3 and 12 months after the neurosurgical treatment. Some degree of hypopituitarism was shown in 16 patients (43.2%) at the 3-months follow-up. Hypogonadism was present in 4 patients, hypoadrenalism in another 4 and hypothyroidism in 2. Two patients showed mild hyperprolactinemia and no patients had diabetes insipidus. Seven patients (18.9%) were GH deficient (peak GH <16.5 microg/dl). At 12 months retesting, some degree of hypopituitarism was confirmed in 8 patients, hypogonadism in 2 and hypothyroidism in one; no patients showed hypoadrenalism and GHD was present in 5. This data suggests that hypopituitarism of various degree may develop in patients who are submitted to neurosurgery for primary brain tumors, even far from hypothalamic-pituitary region.

Traumatic brain injury (TBI) has been associated with hypopituitarism in general and GH deficiency (GHD) in particular; the consequences of this on growth and development are likely to be critical in children and adolescents in the so-called "transition phase". In order to verify the consequences of TBI on pituitary function in the transition phase, we studied a population of adolescents and young adults 3 and 12 months after brain injury [no. = 23, 9 females, 14 males; age: 16-25 yr; body mass index (BMI): 21.9 +/- 0.6 kg/m2]. At 3 months, hypopituitarism was present in 34.6%. Total, multiple and isolated deficits were present in 8.6, 4.3 and 21.7%, respectively. Diabetes insipidus (DI) was present in 8.6% patients and mild hyperprolactinemia in 4.3%. At 12 months, hypopituitarism was present in 30.3%. Total, multiple and isolated deficits were present in 8.6, 4.3 and 17.4%, respectively. DI was present in 4.3% of patients and mild hyperprolactinemia in 4.3%. Total hypopituitarism was always confirmed at retesting. Multiple and isolated hypopituitarism were confirmed in 0/1 and 2/5, respectively. Two/23 patients showed isolated hypopituitarism at 12 months only; 1 patient with isolated at 3 months showed multiple hypopituitarism at retesting. GHD and secondary hypogonadism were the most common acquired pituitary deficits. These results show the high risk of TBI-induced hypopituitarism also in the transition age. Thus it is recommended that pediatric endocrinologists follow-up pituitary function of children and adolescents after brain injuries.

Context: Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are conditions at high risk for the development of hypopituitarism., Objective: The objective of the study was to clarify whether pituitary deficiencies and normal pituitary function recorded at 3 months would improve or worsen at 12 months after the brain injury., Design and Patients: Pituitary function was tested at 3 and 12 months in patients who had TBI (n = 70) or SAH (n = 32)., Results: In TBI, the 3-month evaluation had shown hypopituitarism (H) in 32.8%. Panhypopituitarism (PH), multiple (MH), and isolated (IH) hypopituitarism had been demonstrated in 5.7, 5.7, and 21.4%, respectively. The retesting demonstrated some degree of H in 22.7%. PH, MH, and IH were present in 5.7, 4.2, and 12.8%, respectively. PH was always confirmed at 12 months, whereas MH and IH were confirmed in 25% only. In 5.5% of TBI with no deficit at 3 months, IH was recorded at retesting. In 13.3% of TBI with IH at 3 months, MH was demonstrated at 12-month retesting. In SAH, the 3-month evaluation had shown H in 46.8%. MH and IH had been demonstrated in 6.2 and 40.6%, respectively. The retesting demonstrated H in 37.5%. MH and IH were present in 6.2 and 31.3%, respectively. Although no MH was confirmed at 12 months, two patients with IH at 3 months showed MH at retesting; 30.7% of SAH with IH at 3 months displayed normal pituitary function at retesting. In SAH, normal pituitary function was always confirmed. In TBI and SAH, the most common deficit was always severe GH deficiency., Conclusion: There is high risk for H in TBI and SAH patients. Early diagnosis of PH is always confirmed in the long term. Pituitary function in brain-injured patients may improve over time but, although rarely, may also worsen. Thus, brain-injured patients must undergo neuroendocrine follow-up over time.

Traumatic brain injury (TBI) is one of the main causes of death and disability in young adults, with consequences ranging from physical disabilities to long-term cognitive, behavioural, psychological and social defects. Post-traumatic hypopituitarism (PTHP) was recognized more than 80 years ago, but it was thought to be a rare occurrence. Recently, clinical evidence has demonstrated that TBI may frequently cause hypothalamic-pituitary dysfunction, probably contributing to a delayed or hampered recovery from TBI. Changes in pituitary hormone secretion may be observed during the acute phase post-TBI, representing part of the acute adaptive response to the injury. Moreover, diminished pituitary hormone secretion, caused by damage to the pituitary and/or hypothalamus, may occur at any time after TBI. PTHP is observed in about 40% of patients with a history of TBI, presenting as an isolated deficiency in most cases, and more rarely as complete pituitary failure. The most common alterations appear to be gonadotropin and somatotropin deficiency, followed by corticotropin and thyrotropin deficiency. Hyper- or hypoprolactinemia may also be present. Diabetes insipidus may be frequent in the early, acute phase post-TBI, but it is rarely permanent. Severity of TBI seems to be an important risk factor for developing PTHP; however, PTHP can also manifest after mild TBI. Accurate evaluation and long-term follow-up of all TBI patients are necessary in order to detect the occurrence of PTHP, regardless of clinical evidence for pituitary dysfunction. In order to improve outcome and quality of life of TBI patients, an adequate replacement therapy is of paramount importance.

Objective: Acquired hypopituitarism in adults is obviously suspected in patients with primary hypothalamic-pituitary diseases, particularly after neurosurgery and/or radiotherapy. That brain injuries (BI) can cause hypopituitarism is commonly stated and has been recently emphasized but the management of BI patients does not routinely include neuroendocrine evaluations., Aim: To clarify the occurrence of hypopituitarism in patients after traumatic brain injury (TBI) or subarachnoid haemorrhage (SAH) 3 months after the BI., Subjects and Methods: The occurrence of hypopituitarism in conscious patients after traumatic brain injury [TBI, n = 100, 31 women, 69 men; age 37.1 +/- 1.8 years; body mass index (BMI) 23.7 +/- 0.4 kg/m(2); Glasgow Coma Scale (GCS) 3-15] or subarachnoid haemorrhage [SAH, n = 40, 14 men, 26 wpmen, 51.0 +/- 2.0 years; 25.0 +/- 0.6 kg/m(2); Fisher's scale 1-4] was studied in a multicentre study 3 months after the BI. All patients underwent wide basal hormonal evaluation; the GH/IGF-I axis was evaluated by GHRH + arginine test and IGF-I measurement., Results: In TBI patients, some degree of hypopituitarism was shown in 35%. Total, multiple and isolated deficits were present in 4, 6 and 25%, respectively. Diabetes insipidus was present in 4%. Secondary adrenal, thyroid and gonadal deficit was present in 8, 5 and 17%, respectively. Severe GH deficiency (GHD) was the most frequent pituitary defect (25%). In SAH patients, some degree of hypopituitarism was shown in 37.5%. Despite no total hypopituitarism, multiple and isolated deficits were present in 10 and 27.5%, respectively. Diabetes insipidus was present in 7.5%. Secondary adrenal, thyroid and gonadal deficit was present in 2.5, 7.5 and 12.5%, respectively. Severe GHD was the most frequent defect (25%)., Conclusions: TBI and SAH are conditions associated with high risk of acquired hypopituitarism. The pituitary defect is often multiple and severe GHD is the most frequent defect. Thus neuroendocrine evaluations are always mandatory in patients after brain injuries.

In adults, hypopituitarism and growth hormone deficiency (GHD) should be suspected and diagnosed within an appropriate clinical context. It has been demonstrated that all patients with primary hypothalamic-pituitary diseases before and after any medical intervention (defined as neurosurgery, radiotherapy and medical therapy) are at obvious risk - more than just at high risk - for hypopituitarism (greater than 80% had severe GHD). The same obvious risk applies to patients diagnosed as having congenital or acquired GHD in childhood (between 30% and 50% of patients with severe GHD after retesting). Taking into account the fragility of the infundibular-hypothalamic structure, patients with other common pathological conditions of the central nervous system (CNS), such as traumatic brain injury (TBI), subarachnoid haemorrhage (SAH) or primary brain tumours (BT) with related medical intervention could be at risk for developing hypopituitarism, including GHD. GHD is the first and most common sign of pituitary impairment. Despite the risk of pituitary dysfunction and the results of some studies that these risks are greater than previously believed, neuroendocrine evaluations are still not routinely included as part of the clinical management plan for patients with TBI and SAH. Preliminary results of a multicenter study performed under the auspices of the Italian Society of Endocrinology underscore the high risk of hypopituitarism and GHD under these clinical conditions. Thus, careful screening of pituitary function should always be performed in patients following TBI and SAH.

Traumatic brain injury (TBI) may be associated with impairment of pituitary hormone secretion, which may contribute to long-term physical, cognitive, and psychological disability. We studied the occurrence and risk factors of pituitary dysfunction, including growth hormone deficiency (GHD) in 50 patients (mean age 37.6 +/- 2.4 years; 40 males, age 20-60 years; 10 females, age 23-87 years) with TBI over 5 years. Cranial or facial fractures were documented in 12 patients, and neurosurgery was performed in 14. According to the Glasgow Coma Scale (GCS), 16 patients had suffered from mild, 7 moderate, and 27 severe TBI. Glasgow Outcome Scale (GOS) indicated severe disability in 5, moderate disability in 11, and good recovery in 34 cases. Basal pituitary hormone evaluation, performed once at times variable from 12 to 64 months after TBI, showed hypogonadotrophic hypogonadism in 7 (14%), central hypothyroidism in 5 (10%), low prolactin (PRL) levels in 4 (8%), and high PRL levels in 4 (8%) cases. All subjects had normal corticotrophic and posterior pituitary function. Seven patients showed low insulin-like growth factor-I (IGF-I) levels for age and sex. Results of GHRH plus arginine testing indicated partial GHD in 10 (20%) and severe GHD in 4 (8%) cases. Patients with GHD were older (p <0.05) than patients with normal GH secretion. Magnetic resonance imaging demonstrated pituitary abnormalities in 2 patients; altogether pituitary dysfunction was observed in 27 (54%) patients. Six patients (12%) showed a combination of multiple abnormalities. Occurrence of pituitary dysfunction was 37.5%, 57.1%, and 59.3% in the patients with mild, moderate, and severe TBI, respectively. GCS scores were significantly (p <0.02) lower in patients with pituitary dysfunction compared to those with normal pituitary function (8.3 +/- 0.5 vs. 10.2 +/- 0.6). No relationship was detected between pituitary dysfunction and years since TBI, type of injury, and outcome from TBI. In conclusion, subjects with a history of TBI frequently develop pituitary dysfunction, especially GHD. Therefore, evaluation of pituitary hormone secretion, including GH, should be included in the long-term follow-up of all TBI patients so that adequate hormone replacement therapy may be administered.

Both IGF-I and DHEA-S undergo an age-related decrease and their decrease could be involved in age-related changes in body composition, structure functions and metabolism. On the other hand, it is well known that mean IGF-I levels are clearly reduced in hypopituitaric patients with GH deficiency (GHD) while data about dehydroepiandrosterone sulfate (DHEA-S) levels in hypopituitarism are scanty. We evaluated DHEA-S and IGF-I levels and their relationship in 90 patients with panhypopituitarism (HYPOPIT) with severe GHD [49 women and 41 men; age, mean+/-SE: 47.9+/-1.49 yr, range: 20-80 yr, BMI: 26.4+/-0.6 kg/m2; 21 with childhood-onset (CO) and 69 with adult-onset (AO) HYPOPIT]. DHEA-S and IGF-I levels were also evaluated in 24 HYPOPIT with GHD after 3-month recombinant human GH (rhGH) replacement. Data in HYPOPIT were compared with those in a large group of healthy controls (NS, 233 women and 103 men, aged 20-80 yr; all subjects were within +/-15% of their ideal body weight). In NS both DHEA-S levels and IGF-I were gender-independent while showed a strong, inverse correlation with age (r=-0.6; p<0.001 and r=-0.56; p<0.0001, respectively). Nevertheless, no relationship was found between DHEA-S and IGF-I levels in NS. In HYPOPIT, age-adjusted mean DHEA-S and IGF-I levels were clearly lower than those in NS (2.3+/-0.4 vs 16.0+/-0.7 microg/l, p<0.005; 71.1 +/- 4.5 vs 170+/-4.7 microg/l, p<0.005). IGF-I levels in CO-HYPOPIT were lower (p<0.01) than those in AO-HYPOPIT (49.6+/-4.8 vs 77.0+/-5.4 microg/l), while DHEA-S levels were similar in both subgroups (2.6+/-0.7 vs 2.3+/-0.4 microg/l). In HYPOPIT both DHEA-S and IGF-I were independent of age and gender while there was a trend toward a positive association between each other (r=0.45; p<0.003). Analyzing individual levels in HYPOPIT with respect to age-adjusted normal ranges, IGF-I levels were below normal in 84, 62 and 0% between 20-40, 40-60 and 60-80 yr, respectively. On the other hand, DHEA-S levels were below normal in 84, 86 and 67% between 20-40, 40-60 and 60-80, respectively. In HYPOPIT rhGH treatment strikingly increased IGF-I levels (150+/-3.2 vs 85.3+/-4.1 microg/l, p<0.005) while did not modify DHEA-S levels (1.7+/-0.2 vs 1.6+/-0.2 microg/l). In conclusion, our results demonstrate that DHEA-S and IGF-I are negatively and independently associated to age in physiological conditions but not in hypopituitaric patients in whom both are strikingly reduced. Both DHEA-S and IGF-I levels in HYPOPIT show some overlap with those in normal subjects; thus the assay of these parameters is not diagnostic for hypopituitarism. DHEA-S reduction in HYPOPIT does not depend on IGF-I as indicated also by evidence that GH replacement restores IGF-I but does not modify DHEA-S levels.