Context:

Published data demonstrates that hypopituitarism is common following traumatic brain injury (TBI). Hormone deficiencies are transient in many but the natural history of the acute changes following TBI has not been documented. In addition, it is not clear whether there are any early parameters which accurately predict the development of permanent hypopituitarism.

Objectives:

1. To describe the natural history of plasma cortisol (PC) changes and sodium balance following TBI2. To identify whether acute hypocortisolaemia or cranial diabetes insipidus (CDI) predict mortality3. To identify whether acute pituitary dysfunction predicts the development of chronic anterior hypopituitarism

Design:

Each TBI patient underwent sequential measurement of PC, plasma sodium, urine osmolality and fluid balance following TBI. All other anterior pituitary hormones were measured on day 10 following TBI. The results from 15 surgical comparisons defined a PC < 300nmol/L as inappropriately low for an acutely ill patient. CDI was diagnosed according to the Seckl and Dunger criteria (1). Surviving TBI patients underwent dynamic anterior pituitary testing at least 6 months following TBI.

Setting:

The patients were recruited from the Irish National Neurosurgery Centre.

Patients:

100 sequential TBI patients were recruited. 15 patients admitted to ITU following major surgery were recruited as comparisons.Main Outcome Measures:PC in TBI patients was compared with that of comparisons. Mortality rate was compared between TBI patients with and without acute hypocortisolaemia. Results of follow-up dynamic pituitary testing were compared between those with and without acute hypocortisolaemia.

Results:

78% of TBI patients developed inappropriately low PC following TBI. Low PC and CDI were predictive of mortality. 39% of patients who had follow-up testing had at least one pituitary hormone deficit, all of whom had had previous acute hypocortisolaemia or CDI.

Conclusions:

Acute hypocortisolaemia and CDI are predictive of mortality and long term pituitary deficits in TBI.

OBJECTIVE:

Based on adult data, a peak cortisol ≥500 nmol/L to insulin induced hypoglycaemia constitutes a normal response. Age-specific reference ranges for basal morning cortisol have been developed for clinical use in the paediatric population. Such reference ranges are not clearly established for peak cortisol response to insulin-induced hypoglycaemia despite limited data suggesting an effect of age on peak cortisol. To assess factors affecting the cortisol response to insulin induced hypoglycaemia in children and determine whether peak cortisol was related to age.

DESIGN:

Retrospective cohort study

METHODS:

Retrospective analysis of Children and adolescents ≤18 years undergoing Insulin tolerance Test with adequate hypoglycaemia. Patients with hypopituitarism, severe hypothalamic-pituitary-adrenal axis impairment (peak cortisol <400 nmol/L) or using systemic glucocorticoids were excluded.

RESULTS:

Two hundred and twenty three (223) tests were analysed. Peak cortisol ≥500 nmol/L occurred in 183 (82%) tests. Age was negatively associated with peak cortisol (r = -0.15, p = 0.03). Peak cortisol <500nmol/L was significantly less common in patients <12 years (9/97 (9 %) vs. 31/126 (25 %); p=0.004). In children <12 years the median (5th - 95th centiles) peak cortisol values were 610 (480-806) nmol/L compared to 574 (442 - 789) nmol/L in children ≥12 years (p < 0.004). Similarly, median cortisol increment was significantly higher in younger patients (301 nmol/L compared to 226 nmol/L (p = 0.0004)).

CONCLUSIONS:

Use of a single peak cortisol threshold in children of all ages is not appropriate and will result in over-diagnosis of adrenal insufficiency in adolescents.

OBJECTIVE:

Hypopituitarism is associated with metabolic alterations but in TBI-induced hypopituitarism data are scanty. The aim of our study was to evaluate the prevalence of naïve hypertension, dyslipidemia, and altered glucose metabolism in TBI-induced hypopituitarism patients.

DESIGN:

Cross-sectional retrospective study in a tertiary care endocrinology center. 54 adult patients encountering a moderate or severe TBI were evaluated in the chronic phase (at least 12months after injury) after-trauma. Presence of hypopituitarism, BMI, hypertension, fasting blood glucose and insulin levels, oral glucose tolerance test (if available) and a lipid profile were evaluated.

RESULTS:

The 27.8% of patients showed various degrees of hypopituitarism. In particular, 9.3% had total, 7.4% multiple and 11.1% isolated hypopituitarism. GHD was present in 22.2% of patients. BMI was similar between the two groups. Hypopituitaric patients presented a higher prevalence of dyslipidemia (p<0.01) and altered glucose metabolism (p<0.005) with respect to non hypopituitaric patients. In particular, triglycerides (p<0.05) and HOMA-IR (p<0.02) were higher in hypopituitaric TBI patients.

CONCLUSIONS:

We showed that long-lasting TBI patients who develop hypopituitarism frequently present metabolic alterations, in particular altered glucose levels, insulin resistance and hypertriglyceridemia. In view of the risk of premature cardiovascular death in hypopituitaric patients, major attention has to been paid in those who encountered a TBI, because they suffer from the same comorbidities and may present other deterioration factors due to complex pharmacological treatments and restriction in participation in life activities and healthy lifestyle.

Hypopituitarism has been widely described in adults after traumatic brain injury (TBI); however, the available data in pediatric populations are scarce. Here, we report the results of a prospective, long-term study in children, adolescents and young adults. STUDY GROUP: Thirty-seven children (age, 2 mo to 19.9 yr) out of 51 eligible patients were followed for 1 yr. Clinical and baseline endocrine variables were assessed in all 3 and 12 mo after TBI; children ≥ 6 y underwent two stimulation tests (glucagon stimulation and megatest).

RESULTS:

In the group ≥ 6 y, 11/23 patients (47.8%) had a subnormal GH peak 3 mo after TBI that persisted in 8/23 patients (34%) after one year. The GH response showed no correlation with injury severity (GCS, Marshall classification). Growth velocity was normal in all patients, except for one. Body mass index (BMI) SDS increased significantly in the group with low GH response. A suboptimal cortisol was observed in 10/23 subjects, which normalized in all but three, one year thereafter. All patients but one showed a pubertal response to GnRH testing. No clinical or hormonal abnormalities were detectable in children < 6 yr.

CONCLUSION:

Our results recommend to prospectively follow children after TBI; firstly because the impairment of pituitary function can not be predicted, and secondly, to avoid the potential consequences of pituitary dysfunction. Prospective clinical trials are needed before recommending a systematic screening after TBI, and/or GH therapy either in postpubertal children or in prepubertal children who grow normally. This article is protected by copyright. All rights reserved.

Autoimmune hypophysitis (AH) is commonly believed to be a rare chronic inflammatory condition of the pituitary gland. In clinical practice, however, the disease is often seen indeed. It typically presents with hypopituitarism and pituitary mass found by MRI. We report here unusual presentations of two females with AH followed by empty sella syndrome. The two females, aged at 64 and 57-years-old, presented with anterior pituitary dysfunction, diplopia and diabetes insipidus. By MRI the two patients shared the common characteristics with diffuse homogenous contrast enhancement of the gland and increased stalk thickness. After a long period treatment with glucocorticoids, empty sella was eventually detected by MRI.

PROP-1 gene mutations have been reported as a cause of combined pituitary hormone deficiency. Physical and hormonal phenotypes of affected individuals are variable. We report a 63-year-old female who presented with osteoporosis. She was short, did not enter puberty spontaneously and had primary amenorrhea. Biochemical evaluation revealed secondary hypothyroidism and mixed hyperlipidaemia, while dynamic testing of pituitary function was diagnostic of hypopituitarism. Bone density in the lumbar spine disclosed osteoporosis. DNA analysis showed that the patient was homozygote for the R73H mutation of the PROP-1 gene. The unfavourable long-term course of an untreated patient with PROP-1 gene mutation emphasizes the need for early aetiologic classification and proper management and follow-up of patients with short stature and/or disturbances of pubertal development.

Object Pituitary adenomas are fairly common intracranial neoplasms, and nonfunctioning ones constitute a large subgroup of these adenomas. Complete resection is often difficult and may pose undue risk to neurological and endocrine function. Stereotactic radiosurgery has come to play an important role in the management of patients with nonfunctioning pituitary adenomas. This study examines the outcomes after radiosurgery in a large, multicenter patient population. Methods Under the auspices of the North American Gamma Knife Consortium, 9 Gamma Knife surgery (GKS) centers retrospectively combined their outcome data obtained in 512 patients with nonfunctional pituitary adenomas. Prior resection was performed in 479 patients (93.6%) and prior fractionated external-beam radiotherapy was performed in 34 patients (6.6%). The median age at the time of radiosurgery was 53 years. Fifty-eight percent of patients had some degree of hypopituitarism prior to radiosurgery. Patients received a median dose of 16 Gy to the tumor margin. The median follow-up was 36 months (range 1-223 months). Results Overall tumor control was achieved in 93.4% of patients at last follow-up; actuarial tumor control was 98%, 95%, 91%, and 85% at 3, 5, 8, and 10 years postradiosurgery, respectively. Smaller adenoma volume (OR 1.08 [95% CI 1.02-1.13], p = 0.006) and absence of suprasellar extension (OR 2.10 [95% CI 0.96-4.61], p = 0.064) were associated with progression-free tumor survival. New or worsened hypopituitarism after radiosurgery was noted in 21% of patients, with thyroid and cortisol deficiencies reported as the most common postradiosurgery endocrinopathies. History of prior radiation therapy and greater tumor margin doses were predictive of new or worsening endocrinopathy after GKS. New or progressive cranial nerve deficits were noted in 9% of patients; 6.6% had worsening or new onset optic nerve dysfunction. In multivariate analysis, decreasing age, increasing volume, history of prior radiation therapy, and history of prior pituitary axis deficiency were predictive of new or worsening cranial nerve dysfunction. No patient died as a result of tumor progression. Favorable outcomes of tumor control and neurological preservation were reflected in a 4-point radiosurgical pituitary score. Conclusions Gamma Knife surgery is an effective and well-tolerated management strategy for the vast majority of patients with recurrent or residual nonfunctional pituitary adenomas. Delayed hypopituitarism is the most common complication after radiosurgery. Neurological and cranial nerve function were preserved in more than 90% of patients after radiosurgery. The radiosurgical pituitary score may predict outcomes for future patients who undergo GKS for a nonfunctioning adenoma.

A 10-year-old boy with acute onset cranial diabetes insipidus and multiple autoimmune disorders had evolving panhypopituitarism, thought to be due to autoimmune hypophysitis. Over 18 months, a dramatic clinical course with progressive hypopituitarism and development of type 1 diabetes mellitus was evident. Serial brain imaging showed changes suggestive of germinoma.

Sheehan's syndrome (SS) occurs due to ischemic pituitary necrosis as a result of severe postpartum hemorrhage (PPH).The aim of the present study was to review the presenting features of SS at diagnosis.We retrospectively reviewed 18 cases of SS at diagnosis. Presenting clinical features, laboratory data, pituitary hormone deficiencies, and magnetic resonance imaging (MRI) of the sella were analyzed.Age ranged from 28-71 years with a mean age of 47 ± 14.44 years. Time to diagnosis of SS was 6-33 years with a mean of 15.35 ± 6.74 years. Four (22.2%) patients were referred from emergency for hyponatremia, one each (5.6%) for hypotension, hypoglycemia, and vomiting. Three (16.7%) patients presented with asthenia and weight loss, two (11.1%) with slightly raised thyroid stimulating hormone (TSH). Only six (33.3%) presented with classic features of amenorrhea. None presented with isolated lactational failure or apoplexy after PPH. Seventeen (94.4%) patients had lactational failure; thirteen (72.2%) did not menstruate following last delivery. Lactotroph and gonadotroph failure were present in all at diagnosis but corticotrophs preservation was documented in three (16.7%) and thyrotroph in two (11.1%) patients. Twelve (66.7%) patients had empty sella while six (33.3%) had partial empty sella on MRI.SS has variable features at diagnosis and may present to different specialties. The clinical features of hypopituitarism are often subtle, leading to delay in diagnosis. History of PPH, lactational failure and cessation of menses are important clues. Thyrotroph, corticotroph axis may be preserved in some SS patients.