Clinical impact of hypothalamic-pituitary disorders after conformal radiation therapy for pediatric low-grade glioma or ependymoma.

BACKGROUND: To determine the impact of hypothalamic-pituitary (HP) disorders on health outcomes in children and adolescents who received conformal radiation therapy (RT) for central nervous system tumors. PROCEDURE: Cohort study including 355 patients (age ≤25 years at diagnosis) treated with high-dose (50.4-59.4 Gy) RT using photons for low-grade glioma or ependymoma. Patients (median age, 6.4 years at RT) received systematic endocrine follow-up (median duration, 10.1 years; range, 0.1-19.6). Associations between HP disorders and adverse health outcomes were determined by multivariable analysis. RESULTS: Prevalence was 37.2% for growth hormone deficiency (GHD), 17.7% for gonadotropin deficiency (LH/FSHD), 14.9% for thyroid-stimulating hormone deficiency (TSHD), 10.3% for adrenocorticotropic hormone deficiency (ACTHD), and 12.6% for central precocious puberty (CPP). Hypothalamus mean dose ≥ 36 Gy was associated with higher odds of any deficiency. GHD was associated with short stature (OR 2.77; 95% CI 1.34-5.70), low bone mineral density (OR 3.47; 95% CI 1.16-10.40), and TSHD with dyslipidemia (OR 5.54; 95% CI 1.66-18.52). Patients with ACTHD and CPP had lower intelligence quotient scores, and memory scores were impaired in patients with GHD (P = 0.02). Treatment of GHD was not associated with increased risk for tumor recurrence, secondary tumors, or mortality. CONCLUSIONS: HP disorders occur frequently in patients receiving high-dose RT and are related to physical and neurocognitive well-being. Future studies are needed to assess whether further optimization of endocrine management yields better health outcomes.

Langerhans Cell Histiocytosis Involving Second Cervical Vertebra and the Hypothalamus and Pituitary in an Adult.

BACKGROUND: Adult-onset Langerhans cell histiocytosis (LCH) with simultaneous involvement of the high cervical spine and the hypothalamus is rare. CASE DESCRIPTION: We have reported a case of adult-onset LCH in the second cervical vertebra with bony destruction and subsequent diabetes insipidus due to simultaneous involvement of the hypothalamus and pituitary stalk. Magnetic resonance imaging of the hypothalamus and pituitary lesion and immunohistochemistry of the cervical lesion revealed LCH. Posterior fusion of the cervical spine (first, third, and fourth cervical vertebrae) was performed, followed by systemic chemotherapy. The cervical fusion was well maintained, and the patient achieved clinical remission. No new LCH lesion was found during the follow-up of >2 years. CONCLUSIONS: Patients with known LCH of the spine showing new symptoms of diabetes insipidus should be examined for infiltrating lesions of the pituitary stalk or hypothalamus. In cases of severe instability of the spine, surgical treatment should be performed. If multiple and systemic LCH lesions are found, systemic chemotherapy should be administered.

PITUITARY DEFICIENCY FOLLOWING TRAUMATIC BRAIN INJURY IN EARLY CHILDHOOD: A REVIEW OF THE LITERATURE.

UNLABELLED: AIMS OF REVIEW: the intent of the current manuscript is to critically review the studies on pituitary gland dysfunction in early childhood following traumatic brain injury (TBI), in comparison with those in adults. Search of the literature: The MEDLINE database was accessed through PubMed in April 2015. Results were restricted to the past 15 years and English language of articles. Both transient and permanent hypopituitarisms are not uncommon after TBI. Early after the TBI, pituitary dysfunction/s differ than those occurring after few weeks and months. Growth hormone deficiency (GHD) and alterations in puberty are the most common. After the one to more years of TBI, pituitary dysfunction tends to improve in some patients but may deteriorate in others. GH deficiency as well as Hypogonadism and thyroid dysfunction are the most common permanent lesions. Many of the symptoms of these endocrine defects can pass unnoticed because of the psychomotor defects associated with the TBI like depression and apathy. Unfortunately pituitary dysfunction appear to negatively affect psycho-neuro-motor recovery as well as growth and pubertal development of children and adolescents after TBI. Therefore, the current review highlights the importance of closely following patients, especially children and adolescents for growth and other symptoms and signs suggestive of endocrine dysfunction. In addition, all should be screened serially for possible endocrine disturbances early after the TBI as well as few months to a year after the injury. Risk factors for pituitary dysfunction after TBI include relatively serious TBI (Glasgow Coma Scale score < 10 and MRI showing damage to the hypothalamic pituitary area), diffuse brain swelling and the occurrence of hypotensive and/or hypoxic episodes. IN CONCLUSION: There is a considerable risk of developing pituitary dysfunction after TBI in children and adolescents. These patients should be clinically followed and screened for these abnormalities according to an agreed protocol of investigations. Further multicenter and multidisciplinary prospective studies are required to explore in details the occurrence of permanent pituitary dysfunction after TBI in larger numbers of children with TBI. This requires considerable organisation and communication between many disciplines such as neurosurgery, neurology, endocrinology, rehabilitation and developmental paediatrics.

The infundibulo-tuberal syndrome caused by craniopharyngiomas: clinicopathological evidence from an historical French cohort (1705-1973).

PURPOSE: Infundibulo-tuberal syndrome groups endocrine, metabolic and behavioral disturbances caused by lesions involving the upper neurohypophysis (median eminence) and adjacent basal hypothalamus (tuber cinereum). It was originally described by Henri Claude and Jean Lhermitte in 1917, in a patient with a craniopharyngioma. This study investigates the clinical, pathological and surgical evidence verifying the infundibulo-tuberal syndrome caused by craniopharyngiomas (CPs). METHODS: A systematic retrospective review of craniopharyngiomas reported in French literature between 1705 and 1973 was conducted. A total of 128 well described reports providing a comprehensive clinical and pathological description of the tumors were selected. This series represents the historical French cohort of CPs reported in the pre-CT/MRI era. RESULTS: Three major syndromes caused by CPs were categorized: pituitary syndrome (35%), infundibulo-tuberal syndrome (52%) and hypothalamic syndrome (49%). CP topography was significantly related to the type of syndrome described (p < 0.001). Infundibulo-tuberal syndrome occurred in CPs which replaced or invaded the third ventricle floor. In contrast, the majority of sellar/suprasellar CPs growing below the third ventricle showed a pituitary syndrome (82%). Cases with hypothalamic syndrome were characterized by anatomical integrity of the pituitary gland and stalk (p = 0.033) and occurred predominantly in adults older than 41 years old (p < 0.005). Among infundibulo-tuberal symptoms, abnormal somnolence was not related with the presence of hydrocephalus. All squamous-papillary CPs presented psychiatric disturbances (p < 0.001). CONCLUSION: This historical CP cohort evidences a clinical-topographical correlation between the patient's type of syndrome and the anatomical structures involved by the tumor along the hypophysial-hypothalamic axis.

Morphometry of the pituitary gland and hypothalamus in long-term survivors of childhood trauma.

PURPOSE: Chronic pituitary dysfunction is increasingly recognized as a sequela of traumatic brain injury (TBI). Our aim was to rule out any late morphometric changes of the pituitary gland and hypothalamus in survivors of TBI during childhood requiring intensive care. METHODS: We assessed morphometric abnormalities of the sella region and hypothalamus in patients who sustained TBI during childhood. The patients showed no clinical hormonal dysfunction at the acute phase and pituitary hormone levels at the time of our study were within normal limits. From the 18 enrolled patients in the magnetic resonance study, five were removed due to morphological changes or anatomical variations. We studied the MRI of 13 male survivors (mean age 27 years, mean time after trauma 20 years) and compared them to 13 male control subjects who were matched in terms of age (mean age, 26 years), education and ethnicity. Analyses of the pituitary gland and sella on a midsagittal T2- and T1-weighted image were performed. We used voxel-based morphometry (VBM), an unbiased MRI morphometric method to investigate hypothalamic region in this group of patients. RESULTS: There was only a trend towards a reduced pituitary gland width in the patient group compared to controls. However, no significant morphological and morphometric abnormality was seen and VBM showed no hypothalamic grey matter loss. CONCLUSION: In the absence of hormonal dysfunction, no persisting morphometric changes of the pituitary gland and hypothalamus were seen in survivors of childhood TBI requiring intensive care.

Hypothalamic-pituitary dysfunction in critically ill patients with traumatic and nontraumatic brain injury.

BACKGROUND: A significant number of studies have shown that critically ill patients with brain injury (BI) frequently exhibit abnormal pituitary hormonal responses during the immediate postinjury period. DISCUSSION: The elucidation of endocrine alterations depends on the criteria used, the diagnostic tests applied, and the timing of testing in relation to BI. The pattern of the detected hormonal abnormalities shows considerable variability. Altered endocrine responses are due mostly to hypothalamic changes rather than to pituitary dysfunction. Several studies have examined the correlation between hormonal alterations and BI severity, but the results are inconsistent. Furthermore, it remains currently unclear whether and how pituitary abnormalities adversely affect the clinical course of BI patients during the period of critical illness. On the basis of current knowledge, with the exception of clinically significant relative adrenal deficiency and diabetes insipidus, the other endocrine alterations do not seem to require any therapeutic intervention in severely ill BI patients. It is also uncertain whether hormonal abnormalities detected in the early post-BI period persist for the rest of these patients' lives. CONCLUSIONS: In view of current evidence indicating a high incidence of pituitary dysfunction even years following BI it is recommended that repetition of endocrine evaluation should be performed during the rehabilitation phase in all patients.

Hypothalamopituitary deficiency and precocious puberty following hyperhydration in diabetic ketoacidosis.

We report on a 5-year-old child who survived an intracerebral crisis, following ketoacidosis-revealing diabetes (DKA), with visual impairment due to a vascular occipital lesion. Two and 4 months after the initial episode, a unique hypothalamopituitary disorder consisting in GH, ACTH, TSH deficiencies and central precocious puberty, was detected. Cranial magnetic resonance images showed no visible lesion in the hypothalamopituitary region. The most likely hypothesis is the ischemia of hypothalamopituitary and occipital regions following possible cerebral edema after hyperhydration. She survived with low visual acuteness and received a combined replacement therapy for the neuroendocrinological deficiencies. This case emphasizes that the rehydration at the initial period of DKA is critical, especially when risk factors for cerebral edema are present (young age, marked hyponatremia). The neuroendocrinological consequences of acute cerebral edema are rare, but physicians must be attentive in survivors of these accidents.

Isolated growth hormone deficiency associated with a giant arteriovenous varix.

A 6.5-year-old girl with short stature (height age, 3 years; bone age, 1.75 years) had isolated growth hormone deficiency. Preoperative computed tomography and magnetic resonance imaging demonstrated a large, well-demarcated, homogeneous mass above the dorsum sellae with a density consistent with flowing blood. Vertebral angiography showed a giant intracranial varix caused by an arteriovenous fistula that originated at the apex of the basilar artery. At operation, an aneurysm clip was placed at the origin of the fistula, and occlusion of the fistula was confirmed by intraoperative digital subtraction angiography. There were no permanent neurological sequelae. Despite shrinkage of the varix, demonstrated by follow-up computed tomography, growth hormone deficiency persisted postoperatively. Biosynthetic growth hormone therapy was initiated 6.5 months after surgery and resulted in a height increment of 8.2 cm after 9 months of treatment.

Disorders of endocrine function following cancer therapies.

There is a growing body of literature detailing the endocrine consequences of cancer therapy. Certain conclusions can be drawn from the data presented. Patients who have received incidental hypothalamic--pituitary gland irradiation need to be followed carefully with serial dynamic hormonal evaluations, as they are at high risk of developing growth hormone and prolactin abnormalities and can develop other pituitary tropic hormone deficiencies as well. Children especially should be monitored closely as GH deficiency can be corrected if detected early. Patients who have received radiation to the head and neck region will need long-term (up to 30 years) surveillance for the development of thyroid cancer, hyperparathyroidism or hypothyroidism. Persistent elevations of TSH after incidental thyroidal irradiation are frequently seen and should be reversed with thyroid hormone administration in an attempt to minimize TSH stimulation of the irradiated gland. Radiation to the gonads will cause graded damage dependent on the dose delivered and the mode of fractionation. Age in a woman seems to be a significant factor of radiation sensitivity. Certain chemotherapeutic agents are radiomimetic in their gonadal effects; to date the alkylating agents have been most commonly implicated. FSH elevations herald gonadal damage (aspermia or loss of follicles) and should be looked for in patients receiving abdominal radiation or systemic chemotherapy. Leydig cell dysfunction occurs less frequently. Of all the iatrogenic endocrine complications discussed, some are eminently treatable, and some are quite preventable. Greater awareness of the unexpectedly high incidence of hormonal dysfunction can help lessen therapy-induced morbidity in long-term cancer survivors.

Endocrine morbidity in adults treated with cerebral irradiation for brain tumours during childhood.

Hypothalamic-pituitary function was assessed in 20 adult subjects who were treated with cerebral irradiation for brain tumours during childhood between 8 and 32 years earlier. Nine patients showed impaired growth hormone (GH) responses to hypoglycaemia, of whom, 7 are below the third centile for standing height. All GH deficient subjects received more than 2950 rads to the hypothalamic-pituitary axis with a maximum dose of approximately 5000 rads being used in one case. Three subjects have an elevated basal serum thyroid stimulating hormone (TSH) level and 2 of these show an exaggerated TSH response to thyrotrophin releasing hormone (TRH) but no patient was clinically or biochemically hypothyroid. The rest of hypothalamic-pituitary function was essentially normal. This study shows that multiple pituitary hormone deficiencies do no develop with time when the radiation dose is below a critical level. Thus it appears that there is a gradation of radiation damage to the hypothalamic-pituitary axis which is dependent primarily on the dose received rather than the time interval after radiotherapy.