Posterior Pituitary Dysfunction Research Articles

Impaired Pituitary Axes Following Traumatic Brain Injury.

Pituitary dysfunction following traumatic brain injury (TBI) is significant and rarely considered by clinicians. This topic has received much more attention in the last decade. The incidence of post TBI anterior pituitary dysfunction is around 30% acutely, and declines to around 20% by one year. Growth hormone and gonadotrophic hormones are the most common deficiencies seen after traumatic brain injury, but also the most likely to spontaneously recover. The majority of deficiencies present within the first year, but extreme delayed presentation has been reported. Information on posterior pituitary dysfunction is less reliable ranging from 3%–40% incidence but prospective data suggests a rate around 5%. The mechanism, risk factors, natural history, and long-term effect of treatment are poorly defined in the literature and limited by a lack of standardization. Post TBI pituitary dysfunction is an entity to recognize with significant clinical relevance. Secondary hypoadrenalism, hypothyroidism and central diabetes insipidus should be treated acutely while deficiencies in growth and gonadotrophic hormones should be initially observed.

Burkitt's lymphoma presenting with hypopituitarism: a case report and review of literature.

SummaryHypopituitarism is a rare presentation of Burkitt's lymphoma (BL). The purpose of this report is to present a case of BL presenting with panhypopituitarism and to review other case reports of lymphoma presenting with pituitary dysfunction to highlight the distinguishing features of these cases from other benign aetiologies of pituitary dysfunction such as non-functioning pituitary adenomas. We reviewed a total of 11 cases of lymphoma presenting with pituitary dysfunction published from 1998 to 2013 including the present case. The demographics, clinical presentations, laboratory features, radiological findings, histological diagnosis, treatment administered and outcomes were described. Of the total number of patients, 45.5% of the cases had diffuse large B-cell lymphoma while 27.3% had BL. Anterior pituitary dysfunction was more common than posterior pituitary dysfunction at presentation. The other common associated presenting symptoms were painful ophthalmoplegia, cranial nerve palsies and constitutional symptoms. Hypothalamic–pituitary abnormalities were often demonstrated radiologically to be associated with cavernous sinus and/or stalk involvement. All patients who completed immunochemotherapy responded haematologically. Pituitary dysfunction also improved in most cases although the recovery tended to be partial. In conclusion, a high index of suspicion of underlying malignancy, such as lymphoma, should be present in patients presenting with acute pituitary dysfunction associated with painful ophthalmoplegia, rapidly evolving neurological features, radiological features atypical of a pituitary adenoma and constitutional symptoms. An early diagnosis is essential as prompt initiation of definitive therapy will induce disease remission and recovery of pituitary dysfunction.Learning points Hypopituitarism may be the presenting symptom of lymphoma in the absence of associated overt symptoms or signs of a haematological malignancy resulting in delay in diagnosis and institution of treatment.Pituitary dysfunction due to tumour infiltration has a greater tendency to involve the posterior pituitary and infundibulum resulting in diabetes insipidus and hyperprolactinaemia compared with a non-functioning pituitary adenoma.The common associated symptoms of hypopituitarism due to lymphoma infiltration of the hypothalamic–pituitary system include painful ophthalmoplegia, cranial nerve palsies and constitutional symptoms.Radiological abnormalities of the hypothalamic–pituitary region are usually present and often associated with cavernous sinus or stalk involvement.With early institution of definitive treatment, both haematological response and improvement of pituitary dysfunction are expected although the reversal of hypopituitarism tends to be partial and delayed.A high index of suspicion of underlying malignancy such as lymphoma should be present in patients presenting with acute pituitary dysfunction associated with painful ophthalmoplegia, radiological features atypical of pituitary adenomas and constitutional symptoms to enable early diagnosis and prompt initiation of definitive therapy.

Endocrine and metabolic aspects of the Wolfram syndrome

Wolfram syndrome (WS), also known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness), is a neurodegenerative disease with autosomal recessive inheritance with incomplete penetrance. DIDMOAD is a very rare disease with an estimated prevalence of 1 in 770,000 and it is believed to occur in 1 of 150 patients with juvenile-onset insulin-dependent diabetes mellitus. Additionally, WS may also present with different endocrine and metabolic abnormalities such as anterior and posterior pituitary gland dysfunction. This mini-review summarizes the variable presentation of WS and the need of screening for other metabolic and hormonal abnormalities, coexisting in this rare syndrome.

Sellar-Suprasellar Tuberculomas in Children: 2 Cases and Literature Review

Sellar and suprasellar tuberculomas are rare. Patients with these lesions usually experience headache, vomiting, and hypofunction of pituitary gland; imaging reveals an enhancing sellar-suprasellar mass. We report 2 rare cases of sellar-suprasellar tuberculomas in children aged 8 and 6 years. One child presented with features of headache and vomiting, and the other presented with posterior pituitary dysfunction. In both cases, imaging revealed sellar-suprasellar masses. Both cases were multidrug-resistant tuberculomas. We discuss sellar-suprasellar tuberculomas, a rare form of neurotuberculosis in the background of an overall increase in multidrug-resistant tuberculosis, especially in children.

Sheehan's syndrome with central diabetes insipidus

Sheehan's syndrome refers to the occurrence of hypopituitarism after delivery, usually preceded by postpartum hemorrhage. The condition still continues to be a common cause of hypopituitarism in developing countries like India. The disorder usually presents with anterior pituitary failure with preservation of posterior pituitary functions. Posterior pituitary dysfunction in the form of central diabetes insipidus is rare in patients with Sheehan's syndrome. We describe the clinical course of a young lady who after her sixth childbirth developed severe postpartum hemorrhage followed by development of panhypopituitarism which was confirmed by hormonal investigation and demonstration of empty sella on imaging. In addition, she developed Polyuria. The water deprivation test and response to vasopressin test results indicated central diabetes insipidus. She needed oral desmopressin on a continuous basis to control polyuria.

Radiotherapy in paediatric Cushing’s disease: efficacy and long term follow up of pituitary function

Pituitary radiotherapy (RT) is an effective second-line treatment for paediatric Cushing's disease (CD). We report long-term efficacy and anterior pituitary function in a cohort of paediatric CD patients treated with RT. Between 1988 and 2008, from our cohort of 48 paediatric CD patients, eight paediatric CD patients (5 males and 3 females) underwent second-line pituitary RT (45 Gy in 25 fractions), following unsuccessful transsphenoidal surgery. Out of eight whose long term follow up is available, four patients were cured by RT. Minimum follow up of 2 years is available for all patients. Four patients achieved cure after RT. Two patients were not cured even after follow up of 60 and 132 months, respectively. Out of four uncured patients, two of them had suppressible low dose dexamethasone cortisol with altered circadian rhythm suggesting possibility of response in near future with follow up of just 26 months. Five patients were hypogonadal and one patient was hypothyroid. All patients were below their target height at the time of last follow up. None of the patients had posterior pituitary dysfunction. This series of patients illustrates the efficacy and long-term follow up of pituitary function in children with CD treated with RT. This study also emphasizes the need of growth hormone statues assessment and timely intervention.

The transsphenoidal resection of pediatric craniopharyngiomas: a case series

The majority of pediatric craniopharyngiomas are treated using a transcranial approach. Although there is an increasing acceptance of transsphenoidal resection in adults, there are few reports describing this approach in the pediatric population. The purpose of this study is to report the outcomes after transsphenoidal surgery in a consecutive series of pediatric patients with craniopharyngiomas treated at a single institution with the goal of gross-total resection (GTR). Twenty-three patients with pathologically proven craniopharyngiomas were identified who were 18 years of age or less at the time of surgery. The medical records and imaging studies of the patients were retrospectively reviewed. One patient who was lost to follow-up after surgery was excluded. Among the 22 patients included in the study, 11 underwent transsphenoidal surgery as the primary procedure and 11 underwent transsphenoidal surgery as a secondary procedure after a previous procedure. All patients had at least some sellar component to their tumor and all had either anterior or posterior pituitary dysfunction at presentation. In the entire cohort, a GTR was achieved in 15 (68%) of 22 patients, a radical subtotal resection in 4 (18%) of 22 patients, a subtotal resection in 1 patient, and a partial resection in 2 patients. The degree of resection was higher in the primary transsphenoidal group. After a mean follow-up of 82 months, 4 patients (18%) experienced recurrence. Recurrence occurred in 13% after GTR compared with 28.5% after all other degrees of resection. Tumor recurred in 9% of the primary transsphenoidal group and in 30% of patients who had undergone other therapies prior to the transsphenoidal operation. No patient who had panhypopituitarism experienced a gain of function postoperatively, 67% developed new panhypopituitarism, and 56% experienced new diabetes insipidus. Vision improved or normalized in 9 (64%) of 14 patients presenting with visual loss. Complications included 1 death 3 weeks postoperatively, 2 CSF leaks, and new obesity in 37%. Transsphenoidal resection of pediatric craniopharyngiomas results in a high rate of both visual improvement and GTR with a low associated risk of recurrence. The transsphenoidal approach should be considered in selected pediatric patients with craniopharyngioma, especially those with infradiaphragmatic origin.

Evaluation of development of diabetes insipidus in the early phase following traumatic brain injury in critically ill patients

The purpose of this study was to define the prevalence and outcome of diabetes insipidus (DI) in the early post-traumatic brain injury (TBI) period in ICU patients. Inadequate antidiuretic hormone secretion, which results in DI, is a well recognized complication of TBI, owing to post-traumatic posterior pituitary dysfunction.

Pituitary dysfunction after aneurysmal subarachnoid hemorrhage

Patients recovering from aneurysmal SAH often complain about weakness, fatigue and impaired cognitive skills. Pituitary dysfunction might be one possible reason for these complaints, as in patients with traumatic brain injury, hypopituitarism is known to be a common complication. There are only a few studies dealing with this problem in SAH patients, but these studies suggest that pituitary disturbances are very frequent after aneurysmal SAH. But anterior pituitary lobe disturbances might not be the only one responsible for some complaints or complications in patients suffering from aneurysmal SAH. Hyponatremia in the early state after SAH could be a hint for posterior pituitary lobe dysfunction.

Idiopathic central diabetes insipidus in children and young adults is commonly associated with vasopressin‐cell antibodies and markers of autoimmunity

Autoimmune targeting of hypothalamic-neurohypophyseal structures in children and young adults with posterior pituitary and anterior pituitary dysfunction, as well as pituitary stalk involvement, are not yet completely understood. We aimed to (1) evaluate the presence of circulating vasopressin-cell autoantibodies (AVPc-Abs) in young patients with central diabetes insipidus (CDI), (2) detect organ-specific autoantibodies as markers of autoimmunity, and (3) define the relationship between immune markers and neuroimaging findings. Twenty patients were evaluated at a median age of 16.3 years. Twelve patients had idiopathic CDI, six had Langerhans cell histiocytosis (LCH) and two had germinoma. AVPc-Abs were evaluated in 40 healthy children. Magnetic resonance imaging (MRI) of the hypothalamic-pituitary region was performed longitudinally in all subjects. Circulating arginine vasopressin (AVP), protein tyrosine phosphatase (IA2), glutamic acid decarboxylase (GAD), 21-hydroxylase (21-OH), endomysium antibodies (EMA), parietal cell (PCA), thyroid peroxidase (TPO), thyroglobulin (TG) and TSH-receptor (TSHr) autoantibodies were evaluated. Circulating AVPc-Abs were found in 15 patients (75%), nine with idiopathic CDI, four with LCH and two with germinoma; the pituitary stalk was involved in most of them. Five patients with idiopathic CDI showed a persistence of AVPc-Abs during follow-up and one became positive subsequently. Serum IA2 autoantibodies were demonstrated in 14 patients (70%) and 21-OH autoantibodies in three of them. In idiopathic CDI, circulating AVPc-Abs suggest an autoimmune involvement of the neurohypophyseal system. The identification of AVPc-Abs in subjects who could have either idiopathic CDI or LCH or germinoma, however, indicates that AVPc-Abs cannot be considered a completely reliable marker of autoimmune CDI. Thus, close clinical and MRI follow-up are needed because AVPc-Abs may mask germinoma or LCH.

Magnetic resonance imaging, clinical manifestations, and management of Rathke's cleft cyst

The management of Rathke's cleft cyst (RCC), particularly in patients with no symptoms or with only minor endocrinopathies, has not yet been established. We retrospectively analysed patients with RCC to elucidate correlations between the clinical manifestations, magnetic resonance imaging (MRI) findings, histology and therapeutic outcomes. We retrospectively studied 37 patients with RCC, who underwent computed tomography (CT), MRI and endocrinological examinations, of whom 27 patients underwent surgical intervention. The presence of frontal headaches and anterior pituitary dysfunction was unrelated to the cyst size but was more frequent in patients with high- and isointensity cysts on T1-weighted images (WIs) than those with low-intensity cysts (P=0.0159 and P=0.0249, respectively). All three patients with posterior pituitary dysfunction had a high-intensity cyst on T1-WI (P=0.0385), whereas pituitary dysfunction was not observed in patients with a low-intensity cyst on T1-WI. In contrast to the excellent therapeutic outcomes with regard to visual disturbance and hyperprolactinaemia, recovery of pituitary dysfunction was rare; only three of nine patients with hypopituitarism showed improvement. Among six patients with histologically recognized intense chronic inflammation in the cyst wall, five patients had an RCC of T1 high intensity (P=0.0161), two patients had distinct rim enhancement on MRI (P=0.0060), all patients had frontal headaches (P=0.0130), and four patients had associated hypopituitarism (P=0.0243), none of which improved after surgical intervention. RCCs of high- and isointensity on T1-weighted images, which contain mucous material within the cyst, may be associated with chronic inflammation that can potentially cause irreversible endocrine dysfunction. In asymptomatic patients with RCCs of these MR intensities, close follow-up with precise endocrinological evaluation and gadolinium-enhanced MRI is necessary to avoid occult progression of the inflammation.

The natural history of post-traumatic neurohypophysial dysfunction

Posterior pituitary function remains poorly investigated after traumatic brain injury (TBI). We report the results of a study designed to prospectively define the natural history of post-traumatic diabetes insipidus (DI) and syndrome of inappropriate antidiuretic hormone secretion (SIADH) using standard reliable methodology. 50 consecutive patients with severe or moderate TBI (initial Glasgow Coma Scale (GCS) score 3/15-13/15) were prospectively studied on three occasions: at the acute phase and at 6 months and at 12 months following TBI. In the acute phase, DI was diagnosed either by the presence of hypernatraemia in association with hypotonic polyuria or by the water-deprivation test (WDT) and, at 6 and 12 months by the WDT in all patients. Normative data on response to the WDT were obtained from healthy matched volunteers. Functional outcome was assessed using the Glasgow Outcome Scale (GOS). 13 patients (26%) had DI in the acute post-TBI phase, of whom nine patients recovered by 6 months and one additional patient recovered by 12 months. Of the remaining three patients with permanent DI, two had partial vasopressin deficiency. Acute-phase peak plasma osmolality correlated negatively with the initial GCS scores (r = -0.39, P = 0.005) and with the GOS scores (r = -0.45, P = 0.001). Seven patients had SIADH in the acute phase of TBI but none did at 6 or 12 months. No new cases of DI or SIADH were noted after the acute phase. This prospective study shows that posterior pituitary dysfunction is common following TBI. Most cases recover completely but there is an appreciable frequency of long-term DI which can be subtle and should be recognized and managed appropriately.

Posterior Pituitary Dysfunction after Traumatic Brain Injury

Disorders of water balance are well recognized after traumatic brain injury (TBI), but there are no reliable data on their true prevalence in post-TBI patients. We aimed to evaluate the prevalence of posterior pituitary dysfunction in a large cohort of survivors of TBI. One hundred two consecutive patients (85 males) who suffered severe or moderate TBI were evaluated for diabetes insipidus (DI) at a median of 17 months (range 6-36 months) after the event, using the 8-h water deprivation test (WDT). Their results were compared against normative data obtained from 27 matched, healthy controls. Patients' medical records were retrospectively reviewed for the presence of abnormalities of salt and water balance in the immediate post-TBI period. Twenty-two patients (21.6%) developed DI in the immediate post-TBI period (acute DI group), of whom five had abnormal WDT on later testing. In total, seven patients (6.9%) had abnormal WDT (permanent DI group), five of whom had partial DI. Patients in the acute and permanent DI groups were more likely to have more severe TBI, compared with the rest of the cohort (P < 0.05). In the immediate post-TBI period, 13 patients (12.9%) had syndrome of inappropriate secretion of antidiuretic hormone, which persisted in one patient, and one other patient developed cerebral salt wasting. Diabetes insipidus and syndrome of inappropriate secretion of antidiuretic hormone were common in the immediate post-TBI period. Permanent DI was present in 6.9% of patients who survived severe or moderate TBI, which is higher than traditionally thought. Identification of patients with partial posttraumatic DI is important because appropriate treatment may reduce morbidity and optimize the potential for recovery.

Neuroendocrine dysfunction in the acute phase of traumatic brain injury.

Pituitary hormone abnormalities have been reported in up to 50% of survivors of traumatic brain injury (TBI) who were investigated several months or longer following the event. The frequency of pituitary dysfunction in the early post-TBI period is unknown. To evaluate the prevalence of anterior and posterior pituitary dysfunction in the early phase following TBI. Fifty consecutive patients admitted to the neurosurgical unit with severe or moderate TBI [initial Glasgow Coma Scale (GCS) score 3-13], and 31 matched healthy control volunteers were studied. The glucagon stimulation test (GST) was performed at a median of 12 days (range 7-20) following TBI. Baseline thyroid function, PRL, IGF-1, gonadotrophins, testosterone or oestradiol, plasma sodium, plasma and urine osmolalities or the standard observed water deprivation test were performed. The control subjects underwent the GST for GH and cortisol responses; other parameters were compared to locally derived reference ranges. Control data indicated that peak serum GH of > 5 ng/ml and cortisol > 450 nmol/l following glucagon stimulation should be taken as normal. Nine TBI patients (18%) had GH response < 5 ng/ml (12 mU/l). Eight patients (16%) had peak cortisol responses < 450 nmol/l. Compared to controls, basal cortisol values were significantly lower in patients with subnormal cortisol responses to glucagon and significantly higher in patients with normal cortisol responses (P < 0.05). GH and cortisol deficiencies were unrelated to patient age, BMI, initial GCS or IGF-1 values (P > 0.05). Forty patients (80%) had gonadotrophin deficiency, with low sex steroid concentrations, which was unrelated to the presence of hyperprolactinaemia. In males there was a positive correlation between serum testosterone concentration and GCS (r = 0.32, P = 0.04). One patient had TSH deficiency. Hyperprolactinaemia was present in 26 patients (52%) and serum PRL levels correlated negatively with the GCS score (r =-0.36, P = 0.011). Thirteen patients (26%) had cranial diabetes insipidus (DI) and seven (14%) had syndrome of inappropriate ADH secretion. Our data show that post-traumatic neuroendocrine abnormalities occur early and with high frequency, which may have significant implications for recovery and rehabilitation of TBI patients.

Hypothalamic/pituitary function following high-dose conformal radiotherapy to the base of skull: demonstration of a dose–effect relationship using dose–volume histogram analysis

Purpose: To evaluate the incidence and pattern of hypopituitarism from hypothalamic (HT) and pituitary gland (PG) damage following high-dose conformal fractionated proton–photon beam radiotherapy (PPRT) to the base of skull (BOS) region in adults. The relationship between dose, volume, and PG function is explored. Methods and Materials: Between May 1982 to October 1997, 107 adults with non-PG and non-HT neoplasms (predominantly chordoma and chondrosarcomas) of the BOS were treated with PPRT after subtotal resection(s). The median age was 41.2 years (range, 17–75) with 58 males and 49 females. Median prescribed target dose was 68.4 cobalt gray equivalent (CGE) (range, 55.8–79 CGE) at 1.80–1.92 CGE per fraction per day (where CGE = proton Gy × 1.1). The HT and PG were outlined on planning CT scans to allow dose–volume histograms (DVH) analysis. All patients had baseline and follow-up clinical testing of anterior and posterior pituitary function including biochemical assessment of thyroid, adrenal, and gonadal function, and prolactin secretion. Results: The 10-year actuarial overall survival rate was 87%, with median endocrine follow-up time of 5.5 years, thus the majority of patients were available for long-term follow-up. Five-year actuarial rates of endocrinopathy were as follows: 72% for hyperprolactinemia, 30% for hypothyroidism, 29% for hypogonadism, and 19% for hypoadrenalism. The respective 10-year endocrinopathy rates were 84%, 63%, 36%, and 28%. No patient developed diabetes insipidus (vasopressin deficiency). Growth hormone deficiency was not routinely followed in this study. Minimum target dose (Dmin) to the PG was found to be predictive of endocrinopathy: patients receiving 50 CGE or greater at Dmin to the PG experiencing a higher incidence and severity (defined as the number of endocrinopathies occurring per patient) of endocrine dysfunction. Dmax of 70 CGE or greater to the PG and Dmax of 50 CGE or greater to the HT were also predictive of higher rates of endocrine dysfunction. Conclusion: Radiation-induced damage to the HT & PG occurs frequently after high-dose PPRT to the BOS and is manifested by anterior pituitary gland dysfunction. Hyperprolactinemia was detected in the majority of patients. Posterior pituitary dysfunction, represented by vasopressin activity with diabetes insipidus, was not observed in this dose range. Limiting the dose to the HT and PG when feasible should reduce the risk of developing clinical hypopituitarism.

Dynamic endocrine testing and magnetic resonance imaging in the long-term follow-up of childhood langerhans cell histiocytosis.

Children treated for Langerhans cell histiocytosis (LCH) are at risk for short and long term endocrine sequelae, but biological predictors of specific deficits are not well defined. We evaluated the frequency and progression of LCH-related endocrine deficits during long term follow-up and assessed the ability of dynamic endocrine testing to identify patients at risk for late anterior or posterior pituitary hormone dysfunction. The 17 patients (5 males and 12 females) were followed a median of 10 yr after diagnosis of single system (n = 6) or multisystem (n = 11) disease. Study evaluations, performed a median of 4.1 yr after the diagnosis, comprised pituitary hormone responses to the appropriate challenge, 7-h water deprivation test, 3% hypertonic saline infusion, and magnetic resonance imaging (MRI). The six patients with GH deficiency at the time of evaluation had a significantly lower GH response to GHRH than the other patients [median peak, 7.3 vs. 21.5 micrograms/L (P = 0.03); median area under the curve, 4.7 vs. 13.5 micrograms/L (P = 0.03)]; levels in the latter group did not differ significantly from those in 20 age- and sex-matched controls with constitutional or familial short stature. Two patients who had GH responses to GHRH of 20.6 and 23 ng/mL at 2.8 and 9.5 yr of age developed GH deficiency at 6.5 and 11.2 yr of age, respectively. The TSH response to TRH was less than 10 mU/L in three patients, two of whom later developed central hypothyroidism. ACTH and cortisol responses to CRF, and PRL responses to TRH were normal in all cases, and LH and FSH responses to GnRH were compatible with pubertal stage. Abnormalities in arginine vasopressin responses to water deprivation or hypertonic saline infusion were seen only in four patients who had preexisting diabetes insipidus (DI); one patient who later developed DI had normal findings. On standard MRI, posterior pituitary hyperintensity was absent only in the patients with DI. Pituitary stalk thickening was seen in seven patients, including three who did not have DI and had normal arginine vasopressin responses. Delayed posterior and anterior enhancement on dynamic MRI was present in two patients, both of whom later developed central hypothyroidism. Patients with single system disease had a lower 5-yr probability of LCH reactivation (41% vs. 83% for those with multisystem disease; P = 0.21) and a significantly lower risk of endocrine dysfunction (P = 0.007). In this series, dynamic evaluation of pituitary function was not a useful predictor of late endocrine sequelae, with the possible exception of the progressively decreasing TSH response to TRH. Similarly, a standard MRI was not predictive, although dynamic imaging may be informative regarding evolving pituitary hormone deficiency.

Diabetes insipidus associated with Langerhans cell histiocytosis: is it reversible?

Fourteen of 58 (24%) children with Langerhans cell hisiocytosis (LCH) currently attending the Hospital for Sick Children (London) developed thirst and polyuria during the course of their disease. Three had single-system disease confined to bone, and 11 had multisystem disease. The median age at presentation of LCH was 2 years 0 months, and polyuria/polydipsia developed at a median age of 3 years 9 months (range 1 month before diagnosis of LCH to 4 years after diagnosis). Each child had a water deprivation test with measurement of urinary arginine vasopressin (AVP) to document diabetes insipidus. The doses of 1-desamino-8-D arginine vasopressin (DDAVP) required to control symptoms were compared at diagnosis and at a mean follow-up of 7 years 8 months. Local and systemic treatment was recorded. Ten of 14 children were shown to have "complete" diabetes insipidus, whilest the other four had "partial" diabetes insipidus. Seven children were treated with irradiation. with or without systemic chemotherapy, six with systemic chemotherapy only, and one with DDAVP replacement only. No child, including two with partial diabetes insipidus irradiated within 4 weeks of the onset of symptoms, lost symptoms of polyuria/polydypsia and none was able to discontinue DDAVP replacement. One child treated with Etoposide showed a temporary rise in urinary AVP level to within the normal range but still needed DDAVP to control her symptoms. The mean doses of DDAVP at onset of diabetes insipidus and at follow-up were 9.3 micrograms and 18 micrograms daily, respectively. We conclude that the most appropriate treatment for reversing diabetes insipidus complicating Langerhans cell histiocytosis is yet to be determined. Precise documentation of posterior pituitary dysfunction, including measurement of urinary AVP levels, is essential if the effects of new forms of treatment are to be assessed accurately.

Optic Nerve Hypoplasia: Absence of Posterior Pituitary Bright Signal on Magnetic Resonance Imaging Correlates With Diabetes Insipidus

Magnetic resonance imaging has been used to examine children with optic nerve hypoplasia for pituitary abnormalities who may be at risk for anterior pituitary hormonal deficiencies. We correlated the sellar and optic pathway anatomic findings on magnetic resonance imaging in children with optic nerve hypoplasia with findings from their endocrinologic and ophthalmologic examinations to determine whether magnetic resonance imaging findings predict anterior and posterior pituitary dysfunction. A retrospective review identified five children with optic nerve hypoplasia and endocrinopathy who also underwent high resolution volumetric magnetic resonance imaging. All children had severe bilateral optic nerve hypoplasia and anterior pituitary hormone deficiencies. Three children had no recognizable intrasellar or ectopic posterior pituitary bright spot on magnetic resonance imaging; all had clinical evidence of diabetes insipidus. Two patients with a recognizable but ectopic posterior pituitary did not have diabetes insipidus. Children with optic nerve hypoplasia and no recognizable posterior lobe of the pituitary gland on magnetic resonance imaging are at risk for both anterior and posterior pituitary dysfunction, whereas those with a posterior lobe on magnetic resonance imaging appear to have intact posterior pituitary function.

Two cases of Wegener's granulomatosis involving the pituitary

We describe two patients with Wegener's granulomatosis involving the pituitary. The diagnosis of Wegener's granulomatosis was inferred from the histological appearance of biopsy tissue and the presence of anti-neutrophil cytoplasmic antibodies with cytoplasmic distribution in the first case, in which disease remained confined to the pituitary, causing anterior and posterior pituitary dysfunction. In the second case the diagnosis was made by the progressive involvement of other organ systems, compatible histology and the presence of anti-neutrophil cytoplasmic antibodies with cytoplasmic distribution. In neither patient did posterior pituitary dysfunction respond to immunosuppressive therapy, despite remission of other features of systemic vasculitis. Panhypopituitarism in association with isolated pituitary Wegener's granulomatosis has not previously been described.

Craniopharyngioma: Endocrine Sequelae of Treatment

Following complete surgical resection of a craniopharyngioma, combined anterior and posterior pituitary dysfunction is present in the majority of patients. Moreover, up to three-quarters of the patients will have deficits of four or more hormones. Postsurgery, obesity is common and can be part of a clinical syndrome which includes hyperphagia and normal growth despite GH deficiency. Radiotherapy with or without conservative surgery is associated with fewer endocrine disturbances. Normal growth and sexual development should be possible in most patients with the use of appropriate hormonal substitution therapy.