Diagnosis of Growth Hormone Deficiency in Children: The Efficacy of Glucagon versus Clonidine Stimulation Test.

INTRODUCTION: The diagnosis of childhood growth hormone deficiency (GHD) requires a failure to respond to 2 GH stimulation tests (GHSTs) performed with different stimuli. The most commonly used tests are glucagon stimulation test (GST) and clonidine stimulation test (CST). This study assesses and compares GST and CST's diagnostic efficacy for the initial evaluation of short children. METHODS: Retrospective, single-center, observational study of 512 short children who underwent GHST with GST first or CST first and a confirmatory test with the opposite stimulus in cases of initial GH peak <7.5 ng/mL during 2015-2018. The primary outcome measure was the efficacy of the GST first or CST first in diagnosing GHD. RESULTS: Population characteristics include median age of 9.3 years (interquartile range 6.2, 12.1), 78.3% prepubertal, and 61% boys. Subnormal GH response in the initial test was recorded in 204 (39.8%) children: 148 (45.5%) in GST first and 56 (30%) in CST first, p < 0.001. Confirmatory tests verified GHD in 75/512 (14.6%) patients. Divergent results between the initial and confirmatory tests were more prevalent in GST first than CST first (103/148 [69.6%] vs. 26/56 [46.4%], p < 0.001) indicating a significantly lower error rate for the CST first compared to the GST first. In multivariate analysis, the only significant predictive variable for divergent results between the tests was the type of stimulation test (OR = 0.349 [95% CI 0.217, 0.562], p < 0.001). CONCLUSIONS: Screening of GH status with CST first is more efficient than that with GST first in diagnosing GHD in short children with suspected GHD. It is suggested that performing CST first may reduce the need for a second provocative test and avoid patients' inconvenience of undergoing 2 serial tests.

High prevalence of pituitary dysfunction after aneurysmal subarachnoid hemorrhage: a long-term prospective study using dynamic endocrine testing.

OBJECTIVE: Impaired systemic hormonal activity caused by hypothalamic and pituitary injury may contribute to neuropsychologic disturbances and poor quality of life after aneurysmal subarachnoid hemorrhage (SAH). This prospective study was designed to longitudinally evaluate long-term clinical outcome and pituitary function after SAH using dynamic tests for adrencorticotropic and somatotropic secretory capacity. METHODS: Endocrine function was assessed by basal hormonal concentrations at 6-12 months and 12-24 months after SAH. At the 12-24 months follow-up, dynamic provocative evaluation of adrenocorticotropic hormone (ACTH) and growth hormone (GH) was performed using the insulin tolerance test (ITT). In patients where ITT was contraindicated, an ACTH stimulation test was used to assess ACTH capacity, and a growth hormone releasing hormone (GHRH)-arginine stimulation test was used to assess GH capacity. RESULTS: Of 60 patients with SAH screened, 51 were included in the study, and 44 remained to be tested at the two follow-up visits. As assessed by basal hormone concentrations alone, the prevalence of pituitary dysfunction was 34% at 6-12 months and 41% at 12-24 months. When using dynamic tests (12-24 months), impaired pituitary function was detected in 43%. The ITT detected more cases of central hypoadrenalism and GH deficiency compared with the ACTH- and GHRH-arginine-stimulation tests, respectively. CONCLUSIONS: Application of dynamic endocrine tests revealed a high frequency of long-term hypothalamic-pituitary dysfunction after aneurysmal SAH. The role of pituitary dysfunction in the recovery after SAH merits further evaluation.

The effect of identifying macroprolactinemia on health-care utilization and costs in patients with elevated serum prolactin levels.

OBJECTIVES: The routine screening for macroprolactin of all hyperprolactinemic patients may avoid unnecessary imaging procedures and medication prescription. The study described the frequency and types of tests requested after a diagnosis of high serum prolactin concentration, and assessed whether the diagnosis of macroprolactinemia resulted in lower downstream utilization and costs compared with hyperprolactinemic patients. METHODS: A cost analysis was conducted using a decision tree to model the health-care utilization of the two groups. The database of the Fleury Medicina e Saúde provided the tests and medication of patients with a prolactin value >or=30 microg/L for a period of 6 months. RESULTS: Six hundred fifty-four of 1793 patients (36.5%) had hyperprolactinemia because of macroprolactin. The average number of tests per individual was higher (P = 0.001) in the patients with true hyperprolactinemia (3.07) than in patients with macroprolactinemia (2.51).The average cost in the hyperprolactinemic group (R$425 or euro 162) was significantly higher (P < 0.001) than the macroprolactinemic group (R$340 or euro 130), an incremental cost 25% higher. CONCLUSION: The macroprolactin screening did not completely avoid inappropriate clinical investigation or associated health-care costs. Our results demonstrate the importance of proper medical education and knowledge diffusion of the meaning of macroprolactinemia.

An audit of 500 subcutaneous glucagon stimulation tests to assess growth hormone and ACTH secretion in patients with hypothalamic-pituitary disease.

OBJECTIVE: The insulin tolerance test (ITT) is usually regarded as the 'gold standard' for the assessment of the hypothalamic-pituitary axis (growth hormone (GH) and ACTH) but must be used with caution and is contra-indicated in certain groups of patients. The glucagon stimulation test (GST) has previously been shown to be a good alternative when the ITT is contra-indicated and like the ITT stimulates both GH and ACTH secretion. There is however limited data on the use of the GST in patients with hypothalamic-pituitary disease. DESIGN AND PATIENTS: An audit of 500 GST was performed in 374 patients with hypothalamic-pituitary disease. Glucagon was administered via the subcutaneous route and bloods were taken at times 0 90 120 150 180 210 and 240 minutes. RESULTS: In the vast majority peak GH (84.4%) and cortisol (93%) responses occurred between 120 and 180 minutes Little information was obtained from the 240 minute sample. The medical supervision required was minimal and the side-effects encountered during this test were mild; 20% of the tests were associated with nausea occasionally with vomiting sweating or headaches. Four patients fainted but recovered quickly. CONCLUSIONS: This large audit has shown that the glucose stimulation test is well tolerated and can easily be performed in an out-patient setting with minimal medical supervision. The 240 minute sample added little additional information and could be omitted.

A survey of the current methods used in the UK to assess pituitary function.

A national survey of the current methods used by specialists to evaluate pituitary function in the UK was performed by postal questionnaire. Seventy-three respondents, of whom 89% were consultants and 80% clinical endocrinologists, returned the questionnaire. Fifty per cent routinely used the insulin stress test (IST) to evaluate the hypothalamo-pituitary-adrenal (HPA) axis, while 50% routinely used tetracosactrin stimulation, there being little overlap between the two groups. This represents a significant change in clinical practice since the last survey in 1988. In those who used ACTH stimulation there was almost an equal split into those who administered the tetracosactrin intramuscularly (45%) or intravenously (47%). Furthermore, either the peak or 60 min cortisol value was used by 71% when interpreting the result of the test, despite the fact that in previous studies only the 30 min cortisol value has been shown to correlate with the IST result. The IST remains the most frequently used method to assess growth hormone reserve in adult subjects. The thyrotrophin-releasing-hormone and gonadotrophin-releasing-hormone tests are still used routinely by approximately a quarter of clinicians. These results provide data that could be used to develop guide-lines for the use of tests to investigate pituitary function.