The diagnosis and prevalence of hypoprolactinemia in patients with panhypopituitarism and the effects on depression and sexual functions.

PURPOSE: We aimed to investigate the prevalence and the diagnostic criteria of hypoprolactinemia in patients with panhypopituitarism and the effects of hypoprolactinemia on depression and sexual functions. MATERIALS AND METHODS: Forty-eight patients with panhypopituitarism and 20 healthy volunteers were included. Basal hormone levels were measured and a TRH stimulation test was performed. For the evaluation of sexual functions, questionnaries of Female Sexual Functional Index (FSFI) for females and International Erectile Functional Index for males were performed to the subjects. Depressive symptoms were evaluated by Beck Depression Envontory score (BDI-II). RESULTS: The peak PRL response to TRH stimulation test at 5th percentile in the control group was 18.6 ng/ml in males and 41.6 ng/ml in females and accepted as the cut-offs for sufficient response of PRL. Prolactin was insufficient in 42(87.5%) patients. A basal PRL level of ≤ 5.7 ng/ml in males and 7.11 ng/ml in females was 100% specific in predicting an inadequate response to TRH stimulation test with 80% and 70% sensitivity respectively. A basal PRL level of ≥ 8.5 ng/dl in males was 100% specific and 76% sensitive, and in females a level of ≥ 15.2 ng/dl was 96% specific and 66% sensitive in predicting an adequate response to TRH. PRL deficient patients with panhypopituitarism had higher depression scores compared to the controls, lower sexual function scores in males. CONCLUSION: PRL deficiency is prevalent among individuals with panhypopituitarism, with the potential to result in elevated depression scores in both sexes and impaired sexual functions in males. A basal PRL level seems to be sufficient for the diagnosis of hypoprolactinemia in routine clinical practice.

Machine-Learning Prediction of Postoperative Pituitary Hormonal Outcomes in Nonfunctioning Pituitary Adenomas: A Multicenter Study.

Objective: No accurate predictive models were identified for hormonal prognosis in non-functioning pituitary adenoma (NFPA). This study aimed to develop machine learning (ML) models to facilitate the prognostic assessment of pituitary hormonal outcomes after surgery. Methods: A total of 215 male patients with NFPA, who underwent surgery in four medical centers from 2015 to 2021, were retrospectively reviewed. The data were pooled after heterogeneity assessment, and they were randomly divided into training and testing sets (172:43). Six ML models and logistic regression models were developed using six anterior pituitary hormones. Results: Only thyroid-stimulating hormone (p < 0.001), follicle-stimulating hormone (p < 0.001), and prolactin (PRL; p < 0.001) decreased significantly following surgery, whereas growth hormone (GH) (p < 0.001) increased significantly. The postoperative GH (p = 0.07) levels were slightly higher in patients with gross total resection, but the PRL (p = 0.03) level was significantly lower than that in patients with subtotal resection. The optimal model achieved area-under-the-receiver-operating-characteristic-curve values of 0.82, 0.74, and 0.85 in predicting hormonal hypofunction, new deficiency, and hormonal recovery following surgery, respectively. According to feature importance analyses, the preoperative levels of the same type and other hormones were all important in predicting postoperative individual hormonal hypofunction. Conclusion: Fluctuation in anterior pituitary hormones varies with increases and decreases because of transsphenoidal surgery. The ML models could accurately predict postoperative pituitary outcomes based on preoperative anterior pituitary hormones in NFPA.

Diagnostic value of standard deviation score of log-transformed serum dehydroepiandrosterone sulfate in patients with hypothalamic-pituitary-adrenal axis insufficiency.

Serum dehydroepiandrosterone sulfate (DHEA-S) levels reflect the state of adrenocorticotropic hormone (ACTH) secretion. However, it is difficult to use serum DHEA-S to diagnose hypothalamic-pituitary-adrenal (HPA) axis insufficiency due to its non-normal and highly skewed distribution. In this study, we focused on HPA insufficiency caused by hypothalamic and/or pituitary dysfunction and evaluated the usefulness of the standard deviation score of log-transformed DHEA-S (ln DHEA-S SD score), which was calculated from the established age- and sex-specific reference values. We retrospectively reviewed the medical records of 94 patients suspected of having HPA insufficiency, in whom serum DHEA-S measurement and the rapid ACTH stimulation test were performed, and included 65 patients who met our criteria in this study. The ln DHEA-S SD scores were distributed more normally than measured DHEA-S levels and were significantly higher in patients with a peak cortisol level ≥18 µg/dL than in those below this value, suggesting that this score is a legitimate and strong indicator of adrenocortical function. The optimal cut-off value for impaired HPA function was -0.853, with a sensitivity of 70.3% and a specificity of 100%. Among the 37 patients whose peak cortisol levels were below 18 µg/dL, 11 patients with ln DHEA-S scores ≥-0.853 exhibited significantly higher basal ACTH and basal and peak cortisol levels than the 26 patients with scores <-0.853. Thus, this score plays a supportive role in evaluating HPA axis function, particularly in patients with borderline cortisol responses to ACTH.

High-intensity interval exercise test stimulates growth hormone secretion in children.

BACKGROUND: exercise stimulates growth hormone (GH) secretion and may serve as a promising physiological test for the diagnosis of GH deficiency. However, exercise standardization for a feasible GH test is still lacking. The aim of the present study was to examine the GH secretion to high intensity interval exercise. METHODS: Seventeen children (12.4 ± 2.6 years) with impaired growth rate performed high-intensity interval exercise test (HIIE) that included 10 intervals of 15 s all out pedaling against resistance determined by age, sex and weight on a cycle ergometer with 1-min active rest between each interval. Power output measurements were collected during the test. Blood samples were collected before, immediately after, 30, 45, and 60min after the beginning of the exercise test. GH response was compered to pharmacological provocation test (clonidine or glucagon). RESULTS: HIIE led to a significant increase in GH levels (p < 0.001), with high correlation to GH response following pharmacological stimulation (r = 0.82, r = 0.80 for clonidine and glucagon respectively, p < 0.001) A significant correlation was found between mean peak power to body weight and the GH response (r = 0.50, p = 0.04). 83% of the participants who reached peak power > 10 watts/kg had normal GH secretion. CONCLUSIONS: HIIE is a brief and individualized exercise protocol that may be used as a physiological provocation test for GH secretion. There might be a minimum of anaerobic power needed to induce adequate GH response during HIIE.

The hypothalamus-pituitary-thyroid (HPT)-axis and its role in physiology and pathophysiology of other hypothalamus-pituitary functions.

The hypothalamus-pituitary-thyroid axis is one of several hormone regulatory systems from the hypothalamus to the pituitary and ultimately to the peripheral target organs. The hypothalamus and the pituitary gland are in close anatomical proximity at the base of the brain and extended through the pituitary stalk to the sella turcica. The pituitary stalk allows passage of stimulatory and inhibitory hormones and other signal molecules. The target organs are placed in the periphery and function through stimulation/inhibition by the circulating pituitary hormones. The several hypothalamus-pituitary-target organ axis systems interact in very sophisticated and complicated ways and for many of them the interactive and integrated mechanisms are still not quite clear. The diagnosis of central hypothyroidism is complicated by itself but challenged further by concomitant affection of other hypothalamus-pituitary-hormone axes, the dysfunction of which influences the diagnosis of central hypothyroidism. Treatment of both the central hypothyroidism and the other hypothalamus-pituitary axes also influence the function of the others by complex mechanisms involving both central and peripheral mechanisms. Clinicians managing patients with neuroendocrine disorders should become aware of the strong integrative influence from each hypothalamus-pituitary-hormone axis on the physiology and pathophysiology of central hypothyroidism. As an aid in this direction the present review summarizes and highlights the importance of the hypothalamus-pituitary-thyroid axis, pitfalls in diagnosing central hypothyroidism, diagnosing/testing central hypothyroidism in relation to panhypopituitarism, pointing at interactions of the thyroid function with other pituitary hormones, as well as local hypothalamic neurotransmitters and gut-brain hormones. Furthermore, the treatment effect of each axis on the regulation of the others is described. Finally, these complicating aspects require stringent diagnostic testing, particularly in clinical settings with lower or at least altered à priori likelihood of hypopituitarism than in former obvious clinical patient presentations.

Characteristics of Patients with Hypopituitarism having Onset Symptoms of Pseudo-Intestinal Obstruction: A Case Report.

BACKGROUND: Gastrointestinal symptoms are often the first symptoms of hypopituitarism. However, pseudo-intestinal obstruction is not a common manifestation of hypopituitarism. Some patients presenting with gastrointestinal symptoms as their chief complaint were admitted to the Department of Gastroenterology and were accurately diagnosed with hypopituitarism at the Department of Endocrinology. CASE SUMMARY: This case pertains to a 57-year-old man with poor appetite, fatigue, weakness, and recent onset recurring abdominal pain. An erect, abdominal X-ray indicated flatulence and gas-fluid levels in the midsection of the abdomen, and pseudo-intestinal obstruction was diagnosed. Subsequently, the patient was referred to the Department of Gastroenterology to identify the cause of the pseudo-intestinal obstruction. An examination of the digestive system did not reveal any abnormalities, but the patient developed hyponatremia and exhibited drowsiness. The patient was transferred to the Department of Endocrinology for further treatment. The patient was eventually diagnosed with hypopituitarism, caused by empty sella syndrome. The patient received prednisone and euthyrox replacement therapy, and pseudo-intestinal obstruction did not occur again. CONCLUSION: In general, endocrine diseases, including hypopituitarism, hypothyroidism, and hyponatremia, should be considered for patients with pseudo-intestinal obstruction combined with hyponatremia and drowsiness, especially if the symptoms of the digestive system are not complicated and the drowsiness is obvious.

Lower Oxytocin Levels Are Associated with Lower Bone Mineral Density and Less Favorable Hip Geometry in Hypopituitary Men.

INTRODUCTION: Hypopituitary patients are at risk for bone loss. Hypothalamic-posterior pituitary hormones oxytocin and vasopressin are anabolic and catabolic, respectively, to the skeleton. Patients with hypopituitarism may be at risk for oxytocin deficiency. Whether oxytocin and/or vasopressin contribute to impaired bone homeostasis in hypopituitarism is unknown. OBJECTIVES: To determine the relationship between plasma oxytocin and vasopressin levels and bone characteristics (bone mineral density [BMD] and hip structural analysis [HSA]) in patients who have anterior pituitary deficiencies only (APD group) or with central diabetes insipidus (CDI group). METHODS: This is a cross-sectional study. Subjects included 37 men (17 CDI and 20 APD), aged 20-60 years. Main outcome measures were fasting plasma oxytocin and vasopressin levels, and BMD and HSA using dual X-ray absorptiometry. RESULTS: Mean BMD and HSA variables did not differ between the CDI and APD groups. Mean BMD Z-scores at most sites were lower in those participants who had fasting oxytocin levels below, rather than above, the median. There were positive associations between fasting oxytocin levels and (1) BMD Z-scores at the spine, femoral neck, total hip, and subtotal body and (2) favorable hip geometry and strength variables at the intertrochanteric region in CDI, but not APD, participants. No associations between vasopressin levels and bone variables were observed in the CDI or ADP groups. CONCLUSIONS: This study provides evidence for a relationship between oxytocin levels and BMD and estimated hip geometry and strength in hypopituitarism with CDI. Future studies will be important to determine whether oxytocin could be used therapeutically to optimize bone health in patients with hypopituitarism.

Type 4B hereditary hemochromatosis due to heterozygous p.D157A mutation in SLC40A1 complicated with hypopituitarism.

Hemochromatosis is a clinical syndrome characterized by iron overload in various organs. We present here a case of type 4 hereditary hemochromatosis due to heterozygous mutation in SLC40A1 gene (p.D157A). SLC40A1 encodes ferroportin, a macromolecule only known as iron exporter from mammalian cells. He first presented symptoms correlated with hypopituitarism. Furthermore, marked hyperferritinemia and high transferrin saturation were revealed in combination with the findings of iron overload in the liver, spleen and pituitary gland by computed tomography and magnetic resonance imaging. Liver biopsy revealed iron deposition in both hepatocytes and Kupffer cells. SLC40A1 mutations are considered to cause wide heterogeneity by various ferroportin mutations. Thus, clinicopathological examinations seem to be very important for diagnosing phenotype of type 4 hemochromatosis in addition to the gene analysis. We diagnosed him as type 4B hereditary hemochromatosis (ferroportin-associated hemochromatosis) by the findings of high transferrin saturation and iron deposition in hepatocytes, and then started iron chelating treatment. We should suspect the possibility of hereditary hemochromatosis even in Japanese with severe iron overload. Although the same mutation in SLC40A1 gene (p.D157A) had been reported to cause "loss of function" phenotype, we considered that the mutation of our case caused "gain of function" phenotype.

Central diabetes insipidus unveiled by glucocorticoid therapy in a patient with an empty sella: A case report and literature review.

RATIONALE: Some diseases contribute to hypopituitarism without clinical manifestations and the glucocorticoid therapy may unveil central diabetes insipidus. The condition is rare and usually causes problems for clinical physicians. PATIENT CONCERNS: A 59-year-old woman presented to our hospital due to facial numbness and persistent eyelid heaviness. DIAGNOSIS: Physical examination and cerebrospinal fluid examination supported a diagnosis of Guillain-Barre[Combining Acute Accent] syndrome. Magnetic resonance imaging showed an empty sella. Hormone test indicated hypopituitarism. INTERVENTIONS: The patient received intravenous immunoglobulin and glucocorticoid. Central diabetes insipidus appeared after 20 days. Subsequently, the patient was prescribed 1-desamino-8-D-arginine vasopressin and prednisone. OUTCOMES: During 6 months' follow-up, the patient's urine output was gradually reduced to normal level. LESSONS: This case indicated that hypopituitarism may be caused by an empty sella and be masked by adrenal insufficiency. Central diabetes insipidus may present after glucocorticoid therapy.

Evaluation of oxidative stress effects on different macromolecules in adult growth hormone deficiency.

Adult growth hormone deficiency (GHD) is being increasingly recognized to cause premature mortality exacerbated by oxidative stress. A case-control observational study has been performed with the primary objective of evaluating new parameters of oxidative stress and macromolecular damage in adult GHD subjects: serum nitrotryptophan; Total Antioxidant Capacity expressed as LAG time; urinary hexanoil-lysine; urinary dityrosine and urinary 8-OH-deoxyguanosine. GHD was diagnosed using Growth Hormone-Releasing Hormone 50µg iv+arginine 0,5 g/Kg test, with a peak GH response <9 µg /L when BMI was <30 kg/m2 or <4 µg/L when BMI was >30 kg/m2. Patients affected by adult GHD were divided into three groups, total GHD (n = 26), partial GHD (n = 25), and controls (n = 29). Total Antioxidant Capacity, metabolic and hormonal parameters have been determined in separate plasma samples; nitrotryptophan in serum samples; hexanoil-lysine, dityrosine, 8-OH-deoxyguanosine in urine samples. Assessment of hexanoil-lysine exhibited a trend to increase in comparing total GHD vs partial and controls, although not significant. Values of 8-OH-deoxyguanosine did not significantly differ among the three groups. Significant lower levels of dityrosine in partial GHD vs total and controls were found. No significant difference in nitrotriptophan serum levels was found, while significantly greater values of Total Antioxidant Capacity were showed in total and partial GHD vs controls. Thus, our result confirm that oxidative stress is increased both in partial and total adult GHD. The lack of compensation by antioxidants in total GHD may be connected to the complications associated to this rare disorder.

Masked type 1 diabetes mellitus (T1DM) unveiled by glucocorticoid replacement: a case of simultaneous development of T1DM and hypophysitis in an elderly woman.

As a rare condition characterized by inflammation of the pituitary gland, hypophysitis usually results in hypopituitarism and pituitary enlargement. The most critical outcome of hypopituitarism is caused by secondary adrenal insufficiency. Glucocorticoid deficiency is a life-threatening condition, and patients who develop this deficiency require prompt diagnosis and treatment. However, a delayed diagnosis of hypopituitarism may occur due to its non-specific clinical manifestations. A common presenting sign of glucocorticoid deficiency is hypoglycemia. The amelioration of hyperglycemia has been observed in diabetic patients with adrenal insufficiency. We report the case of a 70-year-old Japanese woman who had suffered from fatigue and anorexia for several months; she was admitted based on refractory hyponatremia (sodium 125-128 mEq/L) and hypoglycemia (glucose 58-75 mg/dL). Laboratory findings and magnetic resonance imaging findings led to the diagnosis of panhypopituitarism caused by autoimmune hypophysitis. After receiving 10 mg/day of hydrocortisone, the patient developed severe hyperglycemia (glucose >500 mg/dL). Undetectable C-peptide levels and positive results of both insulinoma-associated antigen-2 antibodies and insulin autoantibodies indicated that she had experienced a recent onset of type 1 diabetes. The pathophysiological process indicated that overt hyperglycemia could be masked by the deficient action of glucocorticoids even in a diabetic patient with endogenous insulin deficiency. This uncommon case reinforces the importance of the prompt diagnosis and treatment of hypopituitarism. Clinicians should remain aware of the possibility of hidden diabetes when treating hypoglycemia in patients with adrenal insufficiency.

Metabolic syndrome and its components in adult hypopituitary patients.

PURPOSE: To evaluate the prevalence of metabolic syndrome (MetS) and its components in adult hypopituitary patients. PATIENTS AND METHODS: Retrospective, cross-sectional analysis of a cohort of hypopituitary adult patients followed in a single reference center for pituitary diseases. MetS was defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. Patients with 18 years or older, presenting two or more anterior pituitary deficiencies associated or not with diabetes insipidus (DI), were included, while patients with hypopituitarism due to Acromegaly or Cushing's disease were excluded. RESULTS: We studied 99 hypopituitary patients (52 males, mean age 50.1 ± 16.3 years, mean age at diagnosis 33.7 ± 17.6 years) who have been followed for a mean time of 15.9 ± 10.1 years. Hypothalamic-pituitary tumors and non-tumoral etiologies were observed in 53.4% and 46.6% of the cases, respectively. FSH/LH, GH, TSH, ACTH deficiency and DI was present in 99%, 98.6%, 96%, 81.8%, and 23.2%, respectively. The prevalence of MetS was 39.4% and was significantly higher in patients older than 50 years (p = 0.02), overweight/obese (p < 0.001), with hypopituitarism diagnosed in adult life (p = 0.02), who did not replace GH (p = 0.004) and in smokers (p = 0.007). In the logistic regression model, body mass index (BMI) and GH replacement were significantly associated with the presence of MetS. Reduced HDL cholesterol was the most prevalent component of MetS in hypopituitary patients. CONCLUSIONS: MetS is a common finding in adult hypopituitary patients, which is mainly influenced by increased BMI and untreated GH deficiency. Trial Registration number (Plataforma Brasil): CAAE 51008815.2.0000.0096 (May 31, 2017) .

The Optimized Calculation Method for Insulin Dosage in an Insulin Tolerance Test (ITT): A Randomized Parallel Control Study.

Objective: To explore the most suitable calculation method for insulin dosage in an insulin tolerance test (ITT) and to evaluate the clinical application value of the optimization coefficient (γ). Methods: In this study, 140 adult patients with congenital growth hormone deficiency (GHD) or acquired hypopituitarism were randomized into the following two groups: the conventional group (n = 70) and the optimized group (n = 70). Oral glucose tolerance tests (OGTTs), insulin release tests (IRTs), and ITTs were conducted. For ITTs, insulin doses were the product of body weight (kg) and related coefficient (0.15 IU/kg for the control group and γ IU/kg for the optimized group, respectively). Notably, γ was defined as -0.034 + 0.000176 × AUCINS + 0.009846 × BMI, which was based on our previous study. Results: In the ITTs, the rate of achieving adequate hypoglycemia with a single insulin dose was significantly higher for the optimized group compared with the conventional group (92.9 vs. 60.0%, P < 0.001). The optimized group required higher initial doses of insulin (0.23 IU/kg). Meanwhile, the two groups did not differ significantly in their nadir blood glucose (1.9 vs. 1.9 mmol/L, P = 0.828). Conclusion: This study confirmed that the proposed optimized calculation method for insulin dosage in ITTs led to more efficient hypoglycemia achievement, without increasing the incidence of serious adverse events.

Hypopituitarism manifesting after invasive dental treatment in a patient with carcinoma of the tongue: a case report.

BACKGROUND: The symptoms of hypopituitarism are not usually discussed in the clinical setting of oral surgery. CASE PRESENTATION: We herein report a case of hypopituitarism that became evident after biopsy and extraction of several teeth in a 68-year-old man with tongue cancer. Three days after biopsy, the patient developed nausea and vomiting, and his serum sodium had fallen to 124 mEq/L. His serum cortisol concentration was low. Although the plasma concentration of adrenocorticotropic hormone (ACTH) was within the normal range, ACTH stimulation testing showed a lack of cortisol response. Given these findings, we suspected secondary adrenal insufficiency. To investigate the cause of secondary adrenal insufficiency, MRI of the head was performed, which revealed pituitary gland atrophy. The results of pituitary anterior lobe hormone-stimulation tests were compatible with hypopituitarism. Thirty days after biopsy, partial tongue resection was successfully performed under general anesthesia with perioperative hydrocortisone supplementation. CONCLUSIONS: We must be aware of various signs of hypopituitarism when we perform invasive dental treatment.

Cardiovascular effects of growth hormone (GH) treatment on GH-deficient adults: a meta-analysis update.

BACKGROUND: It is still unclear whether growth hormone (GH) replacement is able to improve cardiovascular parameters in adults with GH deficiency (AGHD) from the updated clinical trials reported to date. METHODS AND RESULTS: We systematically reviewed clinical trials of GH treatment on AGHD patients in recent decade, and evaluated the effects of GH on cardiovascular parameters assessed by echocardiography. 11 clinical trials were identified in 3 bibliographic databases. We conducted a combined analysis of effects on four aspects: General indicators: baseline heart rate (BHR), peak heart rate (PHR), systolic blood pressure (SBP), diastolic blood pressure (DBP); Cardiac structure: left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), left ventricular interventricular septum (LVIS), left ventricular mass (LVM), left ventricular posterior wall (LVPW); Cardiovascular function: deceleration time of E wave (DT), E/A ratio (E/A), ejection fraction (EF), NT-BNP; Life quality: peak VO2, VE/VCO2 slope. Overall effect size was used to evaluate significance, and weighted mean difference after GH treatment was given to appreciate size of the effect. GH treatment was associated with a significant increase in BHR (3.03[2.00, 4.06]), LVIS (0.50[0.43, 0.57]), LVPW (0.50[0.43, 0.57]), and EF (2.12[1.34, 2.90]). Overall effect sizes were negative significant for DBP (- 1.19[- 2.33, - 0.05]), LVEDV (- 9.84[- 16.53, - 3.15]), NT-BNP (- 206.34[- 308.95, - 103.72]), and VE/VCO2 slope (- 2.31[- 2.92, - 1.71]). CONCLUSIONS: As assessed by echocardiography, GH administration may improve the general vital signs and life quality of AGHD patients, based on the positive effect on BHR and negative effects on DBP and VE/VCO2 slope. Also, GH treatment would influence the structure of heart with positive effects on LVIS, LVPW and negative effect on LVEDV, which together with the increase of EF and decrease of NT-BNP, then resulting in improving the systolic function of AGHD patients.

Neuroendocrine function and associated mental health outcomes following mild traumatic brain injury in OEF-deployed service members.

Mild traumatic brain injury (mTBI) has been linked to mental health disorders (MHDs) and pituitary function alterations. Due to the complex relationship of mTBI, the neuroendocrine system, and MHDs, we propose that neuroendocrine dysfunction (NED) may play a role in negative long-term health outcomes. The goal of this study was to determine if blast-concussed service members (SMs) have a stronger likelihood of developing NED. We hypothesized that NED either pre- or post-injury is associated with poor mental and physical health outcomes. Serum samples from the Armed Forces Health Surveillance Branch were obtained from concussed (n = 59) and non-concussed (n = 72) SMs treated at the Concussion Restoration Care Center (CRCC) in Afghanistan. Serum was collected within 2 years prior to deployment and one or two times within 3 years following their CRCC visit. Samples were analyzed for luteinizing hormone (LH), testosterone, human growth hormone, cortisol, and prolactin to assess post-injury neuroendocrine function. Results indicate that SMs who incurred an mTBI exhibited long-term LH and testosterone deficiencies 3 years following injury compared to controls. Specifically, 47.6% of head-injured SMs displayed hypofunction in at least one of five hormones at 3 years post-injury. Anxiety disorders were the most common MHD observed in concussed SMs with hypopituitarism, while there was also a trend for SMs with chronic pituitary dysfunction to have MHD diagnoses. Findings indicate blast-related mTBI may be associated with long-term health outcomes following a period of incubation. Neuroendocrine screenings may increase treatment opportunities, inform rehabilitation strategies, and improve overall quality of life for patients.

Ghrelin Does Not Directly Stimulate Secretion of Glucagon-like Peptide-1.

CONTEXT: The gastrointestinal hormone ghrelin stimulates growth hormone secretion and appetite, but recent studies indicate that ghrelin also stimulates the secretion of the appetite-inhibiting and insulinotropic hormone glucagon-like peptide-1 (GLP-1). OBJECTIVE: To investigate the putative effect of ghrelin on GLP-1 secretion in vivo and in vitro. SUBJECTS AND METHODS: A randomized placebo-controlled crossover study was performed in eight hypopituitary subjects. Ghrelin or saline was infused intravenously (1 pmol/min × kg) after collection of baseline sample (0 min), and blood was subsequently collected at time 30, 60, 90, and 120 minutes. Mouse small intestine was perfused (n = 6) and GLP-1 output from perfused mouse small intestine was investigated in response to vascular ghrelin administration in the presence and absence of a simultaneous luminal glucose stimulus. Ghrelin receptor expression was quantified in human (n = 11) and mouse L-cells (n = 3) by RNA sequencing and RT-qPCR, respectively. RESULTS: Ghrelin did not affect GLP-1 secretion in humans (area under the curve [AUC; 0-120 min]: ghrelin infusion = 1.37 ± 0.05 min × nmol vs. saline infusion = 1.40 ± 0.06 min × nmol [P = 0.63]), but induced peripheral insulin resistance. Likewise, ghrelin did not stimulate GLP-1 secretion from the perfused mouse small intestine model (mean outputs during baseline/ghrelin infusion = 19.3 ± 1.6/25.5 ± 2.0 fmol/min, n = 6, P = 0.16), whereas glucose-dependent insulinotropic polypeptide administration, used as a positive control, doubled GLP-1 secretion (P < 0.001). Intraluminal glucose increased GLP-1 secretion by 4-fold (P < 0.001), which was not potentiated by ghrelin. Finally, gene expression of the ghrelin receptor was undetectable in mouse L-cells and marginal in human L-cells. CONCLUSIONS: Ghrelin does not interact directly with the L-cell and does not directly affect GLP-1 secretion.

Distinct pituitary hormone levels of 184 Chinese children and adolescents with multiple pituitary hormone deficiency: a single-centre study.

BACKGROUND: Pituitary tumors and/or their treatment are associated with multiple pituitary hormone deficiency (MPHD) in adults, but the distinct pituitary hormone profile of MPHD in Chinese children and adolescents remains unclear. METHODS: Patients with MPHD were divided into four groups according to their MRI results: 1) pituitary stalk interruption syndrome (PSIS); 2) hypoplasia; 3) normal; and 4) tumor survivor. RESULTS: Among the 184 patients, 93 patients (50.5%) were with PSIS, 24 (13.0%) had hypoplastic pituitary gland, 10 (5.4%) patients were normal, and 57 (31.0%) were tumor survivors. There was an association between abnormal fetal position and PSIS (P ≤ 0.001). The CA/BA in PSIS, hypoplasia, normal, tumor survivor groups were 2.27 ± 1.05, 1.48 ± 0.39, 1.38 ± 0.57, 1.49 ± 0.33, and HtSDS were - 3.94 ± 1.39, - 2.89 ± 1.09, - 2.50 ± 1.05, - 1.38 ± 1.63. Patients in PSIS group had the largest CA/BA (P ≤ 0.001 vs. hypoplasia group, P = 0.009 vs. normal group, P ≤ 0.001 vs. tumor survivors) and lowest HtSDS (P ≤ 0.001 vs. hypoplasia group, P = 0.003 vs. normal group, P ≤ 0.001 vs. tumor survivors). The levels of TSH in the PSIS, hypoplasia, normal, and tumor survivor groups were 1.03 ± 1.08 (P = 0.149 vs. tumor survivors), 1.38 ± 1.47 (P = 0.045 vs. tumor survivors), 2.49 ± 1.53 (P < 0.001 vs. tumor survivors), and 0.76 ± 1.15 µIU/ml. The levels of GH peak in PSIS, hypoplasia, normal, tumor survivor groups were 1.37 ± 1.78, 1.27 ± 1.52, 3.36 ± 1.79, 0.53 ± 0.52 ng/ml and ACTH were 27.50 ± 20.72, 25.05 ± 14.64, 34.61 ± 59.35, 7.19 ± 8.63 ng/ml. Tumor survivors had the lowest levels of GH peak (P ≤ 0.001 vs. PSIS group, P = 0.002 vs. hypoplasia group, P ≤ 0.001 vs. normal group) and ACTH (all the P ≤ 0.001 vs. the other three groups). CONCLUSION: The frequency of PSIS is high among children and adolescents with MPHD. The severity of hormone deficiencies in patients with MPHD was more important in the tumor survivor group compared with the other groups.