Management of children and young people with idiopathic pituitary stalk thickening, central diabetes insipidus, or both: a national clinical practice consensus guideline.

Unexplained or idiopathic pituitary stalk thickening or central diabetes insipidus not only harbours rare occult malignancies in 40% of cases but can also reflect benign congenital defects. Between 2014 and 2019, a multidisciplinary, expert national guideline development group in the UK systematically developed a management flowchart and clinical practice guideline to inform specialist care and improve outcomes in children and young people (aged <19 years) with idiopathic pituitary stalk thickening, central diabetes insipidus, or both. All such cases of idiopathic pituitary stalk thickening and central diabetes insipidus require dynamic pituitary function testing, specialist pituitary imaging, measurement of serum ß-human chorionic gonadotropin and alpha-fetoprotein concentrations, chest x-ray, abdominal ultrasonography, optometry, and skeletal survey for occult disease. Stalk thickening of 4 mm or more at the optic chiasm, 3 mm or more at pituitary insertion, or both, is potentially pathological, particularly if an endocrinopathy or visual impairment coexists. In this guideline, we define the role of surveillance, cerebrospinal fluid tumour markers, whole-body imaging, indications, timing and risks of stalk biopsy, and criteria for discharge. We encourage a registry of outcomes to validate the systematic approach described in this guideline and research to establish typical paediatric stalk sizes and the possible role of novel biomarkers, imaging techniques, or both, in diagnosis.

Neuroendocrine Dysfunction in the Acute Setting of Penetrating Brain Injury: A Systematic Review.

BACKGROUND: Data on neuroendocrine dysfunction (NED) in the acute setting of penetrating brain injury (PBI) are scarce, and the clinical approach to diagnosis and treatment remains extrapolated from the literature on blunt head trauma. METHODS: Three databases were searched (PubMed, Scopus, and Cochrane). Risk of bias was computed using the Newcastle-Ottawa Scale, or the methodological quality of case series and case reports, as indicated. This systematic review was registered in PROSPERO (42020172163). RESULTS: Six relevant studies involving 58 patients with PBI were included. Two studies were prospective cohort analyses, whereas 4 were case reports. The onset of NED was acute in all studies, by the first postinjury day. Risk factors for NED included worse injury severity and the presence of cerebral edema on imaging. Dysfunction of the anterior hypophysis involved the hypothalamic-pituitary-thyroid axis, treated with hormonal replacement, and hypocortisolism, treated with hydrocortisone. The prevalence of central diabetes insipidus was up to 41%. Most patients showed persistent NED months after injury. In separate reports, diabetes insipidus and hypocortisolism showed an association with higher mortality. The available literature for this review is poor, and the studies included had overall low quality with high risk of bias. CONCLUSIONS: NED seems to be prevalent in the acute phase of PBI, equally involving both anterior and posterior hypophysis. Despite a potential association between NED and mortality, data on the optimal management of NED are limited. This situation defines the need for prospective studies to better characterize the clinical features and optimal therapeutic interventions for NED in PBI.

Role of 18F-fluorodeoxyglucose (FDG) and 18F-2-fluorodeoxy sorbitol (FDS) in autoimmune hypophysitis: a case report.

BACKGROUND: Autoimmune hypophysitis is a rare disease characterized by the infiltration of lymphocytic cells into the pituitary gland. 18F-fluorodeoxyglucose (FDG) and 18F-2-fluorodeoxy sorbitol (FDS) positron emission tomography (PET) are well-established and emerging techniques, respectively, which may aid in the diagnosis and classification of autoimmune hypophysitis. CASE PRESENTATION: Here, we report a 40-year-old female diagnosed with central diabetes insipidus and multiple pituitary hormone deficiencies, and MRI revealed homogeneous signals in the pituitary gland as well as thickened in the pituitary stalk. FDG PET localized the pituitary and pituitary stalk lesions and displayed an SUVmax of 5.5. FDS, a sensitive radiotracer for bacterial infections but remains unproven under aseptic inflammation, also demonstrated elevated radioactivity, with an SUVmax of 1.1 at 30 min and 0.73 at 120 min. Transnasal biopsy suggested a diagnosis of autoimmune hypophysitis, and the patient displayed radiological and clinical improvement after treatment with glucocorticoids and hormone replacement. CONCLUSIONS: Autoimmune hypophysitis can display elevated FDG uptake, which aids in the localization of the lesions. In addition to revealing bacterial infection specifically, FDS can also accumulate under autoimmune conditions, suggesting that it could serve as a potential radiotracer for both bacterial and aseptic inflammation. TRIAL REGISTRATION: The patient was enrolled in study NCT02450942 (clinicaltrials.gov, Registered May 21, 2015).

Effect of Arginine on the Hypothalamic-Pituitary-Adrenal Axis in Individuals With and Without Vasopressin Deficiency.

CONTEXT: Arginine stimulates pituitary hormones, like growth hormone and vasopressin, but its effect on the hypothalamic-pituitary-adrenal (HPA) axis is unknown. Arginine may also stimulate the HPA axis, possibly through a mechanism involving vasopressin. OBJECTIVE: To investigate the effect of arginine on adrenocorticotropic hormone (ACTH) and cortisol in subjects with and without vasopressin deficiency. DESIGN: Prospective study, University Hospital Basel. PARTICIPANTS: 38 patients with central diabetes insipidus, 58 patients with primary polydipsia, and 50 healthy controls. INTERVENTION: Arginine infusion with measurement of ACTH, cortisol and copeptin at baseline and 30, 45, 60, 90, and 120 minutes. RESULTS: We found different response patterns to arginine: in patients with diabetes insipidus (and low stimulated copeptin levels) median (interquartile range [IQR]) ACTH and cortisol increased from 22.9 (16.8, 38.7) to 36.6 (26.2, 52.1) ng/L and from 385 (266, 463) to 467 (349, 533) nmol/L, respectively. In contrast, median (IQR) ACTH and cortisol levels decreased in patients with primary polydipsia (despite high stimulated copeptin levels): ACTH from 17.3 (12.3, 23) to 14.8 (10.9, 19.8) ng/L and cortisol from 343 (262, 429) to 272 (220.8, 360.3) nmol/L; likewise, in healthy controls: ACTH from 26.5 (17.6, 35.7) to 14.8 (12.1, 22.7) ng/L and cortisol from 471 (393.3, 581.8) to 301.5 (206.5, 377.8) nmol/L. CONCLUSION: Diabetes insipidus is associated with increased responsiveness of ACTH/cortisol to arginine. In contrast, arginine does not stimulate the HPA axis in healthy controls or in primary polydipsia.

A female with X-linked Nephrogenic diabetes insipidus in a family with inherited central diabetes Insipidus: Case report and review of the literature.

There are two forms of diabetes insipidus, central (neurohypophyseal), and nephrogenic, caused by pathogenic variants in the AVP gene and the AVPR2 or AQP2 genes, respectively. We report on a four-generation family, seven individuals had central diabetes insipidus (CDI) and the female index patient seen from age 16 to 26 years had (mild) nephrogenic diabetes insipidus. In her father with CDI, a known pathogenic heterozygous AVP variant c.232_234del p.(Glu78del) was identified, confirming the diagnosis of CDI in him and the other affected family members. In the proband, molecular analysis disclosed a novel heterozygous AVPR2 gene variant, c.962A > T p.(Asn321Ile) and an extremely skewed X-inactivation, confirming X-linked nephrogenic diabetes insipidus (XL-NDI). Whole exome sequencing showed no further causative mutation. This is the first report on the co-existence of CDI and NDI in one family. Our review of symptomatic female AVPR2 heterozygotes includes 23 families with at least one affected female (including this study). There were 21 different causative mutations. Mutation types in females did not differ from those in males. Both severe XL-NDI and mild forms were reported in females. All six females with severe XL-NDI had complete loss-of-function (null) mutations. The remaining 17 female probands had milder XL-NDI caused by 14 missense variants and three null variants of the AVPR2 gene. X-inactivation was studied in nine of these females; all showed extreme or slight skewing. The review underlines that XL-NDI in female AVPR2 heterozygotes is always accompanied by skewed X-inactivation, emphasizing a need for X-inactivation studies in these females.

Pituitary dysfunction in granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA) is a necrotizing granulomatous vasculitis of small vessels that affect the pituitary gland in less than 1% of cases being exceptionally rare. To describe the clinical, biochemical, radiological findings, treatment, and outcomes of 4 patients with GPA-related hypophysitis. A systematic review of published cases with the same diagnosis is presented as well. A cross-sectional case series of patients with hypophysitis due to GPA from 1981 to 2018 at a third level specialty center. Literature review was performed searching in seven different digital databases for terms "granulomatosis with polyangiitis" and "pituitary gland" or "hypophysitis," including in the analysis all published cases between 1950 and 2019 with a minimum follow-up of 6 months. We found 197 patients with GPA in our institution of whom 4 patients (2.0%) had pituitary involvement. Clinical characteristics and outcomes are described. We also reviewed 7 case series, and 36 case reports describing pituitary dysfunction related to GPA from 1953 to 2019, including the clinical picture of an additional 74 patients. Pituitary dysfunction due to GPA is rare. Treatment is targeted to control systemic manifestations; nevertheless, the outcome of the pituitary function is poor. Central diabetes insipidus, particularly in younger women with other systemic features, should raise suspicion of GPA.Key Points• Involvement of the pituitary gland is an uncommon manifestation in GPA patients. The presence of central diabetes insipidus in the setting of systemic symptoms should prompt its suspicion.• In patients with pituitary involvement due to GPA, affection of other endocrine glands is rare, neither concomitant nor in different times during the disease course. This may arise the hypothesis of a local or regional pathogenesis affection of the gland.• There is no consensus on the best therapy strategy for GPA hypophysitis. Although the use of glucocorticoids with CYC is the most common drug combination, no differences in the outcome of the pituitary function and GPA disease course are seen with other immunosuppressants.• Poor prognosis regarding pituitary function is expected due to possible permanent pituitary tissue damage that results in the need of permanent hormonal replacement.

Endocrine abnormalities in cardiofaciocutaneous syndrome: a case of precocious puberty, hyperprolactinemia and diabetes insipidus.

A 7-year-8-month-old boy with cardiofaciocutaneous syndrome caused by the D638E mutation of the B-Raf proto-oncogene (BRAF) presented with new-onset seizures. He was incidentally found to have advanced Tanner staging on physical examination. Hormonal testing revealed pubertal levels of gonadotropins and sex steroid hormones. On brain imaging, a lack of visualisation of the posterior pituitary bright spot was observed, in addition to mild thinning of the corpus callosum and the lateral gyri of the cerebellar hemispheres. A diagnosis of idiopathic central precocious puberty was made and the patient was started on leuprolide depot treatment. Pituitary hormone testing revealed hyperprolactinemia for which the patient did not receive treatment as he was asymptomatic. During a subsequent hospital admission for seizures, the patient was diagnosed with transient central diabetes insipidus for which he required treatment with a desmopressin infusion.

Engrosamiento del tallo hipofisario en niños y adolescentes con diabetes insípida central: causas y consecuencias / Thickening of the pituitary stalk in children and adolescents with central diabetes insipidus: Causes and consequences

Introducción: La diabetes insípida central (DIC) es una entidad poco frecuente en la edad pediátrica, siendo su etiología heterogénea. El objetivo de nuestro trabajo es demostrar que el seguimiento clínico y neurorradiológico de la región hipotálamo-hipofisaria, puede ayudar a establecer el diagnóstico etiológico de DIC y la presencia de otros déficits hormonales. Métodos: Se revisaron de forma retrospectiva 15 pacientes diagnosticados de DIC en un hospital pediátrico. Se analizaron las características clínicas y auxológicas; así como la valoración de la función adenohipofisaria junto con RM craneal de manera periódica. Resultados: La mediana de edad al diagnóstico fue de 9,6 años (rango: 1,3-15,9). El diagnóstico etiológico pudo establecerse en 9 de los 15 pacientes (germinomas: 7 e histiocitosis: 2). Tras una mediana de seguimiento de 5,5 años (rango: 1,6-11,8), los casos idiopáticos se redujeron a la mitad. Finalmente, los diagnósticos etiológicos fueron: germinoma 9 (60%), histiocitosis 3 (20%) y DIC idiopática 3 (20%). Existe una asociación estadísticamente significativa entre el engrosamiento del tallo y la etiología tumoral. El 67% desarrolló, al menos, una deficiencia hormonal adenohipofisaria, la mayoría en los dos primeros años de seguimiento. El déficit más prevalente fue el de hormona de crecimiento (60%). Conclusiones: En todos los pacientes con DIC se deberá realizar un control auxológico y hormonal, con especial atención, por su frecuencia, a la deficiencia de GH, y en aquellos con DIC idiopática se debería incluir una RM semestral, al menos durante los 2-3 primeros años después del diagnóstico, pues en nuestro estudio el 50% fueron diagnosticados de germinomas o histiocitosis en este periodo

Background: Central diabetes insipidus (CDI) is a rare disorder in children. The aetiology of CDI in childhood is heterogeneous. The aim of this study is to illustrate the importance of a careful clinical and neuro-radiological follow-up of the pituitary and hypothalamus region in order to identify the aetiology and the development of associated hormonal deficiencies. Methods: Clinical and auxological variables of 15 children diagnosed with CDI were retrospectively analysed in a paediatric hospital. Evaluations of adenohypophyseal function and cranial MRI were performed periodically. Results: The mean age at diagnosis of CDI was 9.6 years (range: 1.32-15.9). The aetiological diagnosis could be established initially in 9 of the 15 patients, as 7 with a germinoma and 2 with a histiocytosis. After a mean follow-up of 5.5 years (range: 1.6-11.8), the number of idiopathic cases was reduced by half. At the end of the follow-up, the aetiological diagnoses were: 9 germinoma (60%), 3 histiocytosis (20%), and 3 idiopathic CDI (20%). There is a statistically significant association between stalk thickening and tumour aetiology. At least one adenohypophyseal hormonal deficiency was found in 67% of cases, with the majority developing in the first two years of follow-up. Growth hormone deficiency (60%) was the most prevalent. Conclusion: The follow-up of CDI should include hormone evaluation with special attention, due to its frequency, to GH deficiency. In addition, a biannual MRI in an idiopathic CDI should be performed, at least during the first 2-3 years after diagnosis, as 50% of them were diagnosed with a germinoma or histiocytosis during this period

Endoplasmic reticulum stress induces apoptosis of arginine vasopressin neurons in central diabetes insipidus via PI3K/Akt pathway.

AIMS: Central diabetes insipidus (CDI), a typical complication caused by pituitary stalk injury, often occurs after surgery, trauma, or tumor compression around hypothalamic structures such as the pituitary stalk and optic chiasma. CDI is linked to decreased arginine vasopressin (AVP) neurons in the hypothalamic supraoptic nucleus and paraventricular nucleus, along with a deficit in circulating AVP and oxytocin. However, little has been elucidated about the changes in AVP neurons in CDI. Hence, our study was designed to understand the role of several pathophysiologic changes such as endoplasmic reticulum (ER) stress and apoptosis of AVP neurons in CDI. METHODS: In a novel pituitary stalk electric lesion (PEL) model to mimic CDI, immunofluorescence and immunoblotting were used to understand the underlying regulatory mechanisms. RESULTS: We reported that in CDI condition, generated by PEL, ER stress induced apoptosis of AVP neurons via activation of the PI3K/Akt and ERK pathways. Furthermore, application of N-acetylcysteine protected hypothalamic AVP neurons from ER stress-induced apoptosis through blocking the PI3K/Akt and ERK pathways. CONCLUSION: Our findings showed that AVP neurons underwent apoptosis induced by ER stress, and ER stress might play a vital role in CDI condition through the PI3K/Akt and ERK pathways.

[Thickening of the pituitary stalk in children and adolescents with central diabetes insipidus: Causes and consequences]. / Engrosamiento del tallo hipofisario en niños y adolescentes con diabetes insípida central: causas y consecuencias.

BACKGROUND: Central diabetes insipidus (CDI) is a rare disorder in children. The aetiology of CDI in childhood is heterogeneous. The aim of this study is to illustrate the importance of a careful clinical and neuro-radiological follow-up of the pituitary and hypothalamus region in order to identify the aetiology and the development of associated hormonal deficiencies. METHODS: Clinical and auxological variables of 15 children diagnosed with CDI were retrospectively analysed in a paediatric hospital. Evaluations of adenohypophyseal function and cranial MRI were performed periodically. RESULTS: The mean age at diagnosis of CDI was 9.6 years (range: 1.32-15.9). The aetiological diagnosis could be established initially in 9 of the 15 patients, as 7 with a germinoma and 2 with a histiocytosis. After a mean follow-up of 5.5 years (range: 1.6-11.8), the number of idiopathic cases was reduced by half. At the end of the follow-up, the aetiological diagnoses were: 9 germinoma (60%), 3 histiocytosis (20%), and 3 idiopathic CDI (20%). There is a statistically significant association between stalk thickening and tumour aetiology. At least one adenohypophyseal hormonal deficiency was found in 67% of cases, with the majority developing in the first two years of follow-up. Growth hormone deficiency (60%) was the most prevalent. CONCLUSION: The follow-up of CDI should include hormone evaluation with special attention, due to its frequency, to GH deficiency. In addition, a biannual MRI in an idiopathic CDI should be performed, at least during the first 2-3 years after diagnosis, as 50% of them were diagnosed with a germinoma or histiocytosis during this period.

Central diabetes insipidus: A rare complication of IVH in a very low birth weight preterm infant.

A 710 g male infant was born at a referring hospital at a gestational age of 23 weeks and 2 days via vaginal delivery and was transferred to our facility at 14 days of age. His delivery was complicated by the breech presentation with difficult head extraction. The infant's initial course was significant for respiratory distress syndrome, grade III-IV intraventricular hemorrhage (IVH), acute kidney injury, and large PDA. On the day of life 29, a gradual increase in serum sodium level refractory to increasing total fluid volume was noted. The combination of persistent hypernatremia (150-160 mmol/l), polyuria (8.4 ml/kg/hr), high plasma osmolality (323 mosm/kg), hyposthenuria (75 mosm/kg) and an undetectable serum ADH (<0.8 pg/ml) confirmed the diagnosis of central diabetes insipidus (CDI). Serum sodium and urine output decreased and urine osmolality increased after subcutaneous DDAVP administration.CDI is an uncommon cause of hypernatremia in the neonatal period. The diagnosis can be difficult as excessive urine output and high serum sodium can often be attributed to high insensible water loss in the extremely premature newborn. CDI in our patient was thought to be due to grade III-IV IVH complicated by post-hemorrhagic hydrocephalus.In conclusion, the diagnosis of central DI should be considered as a complication of severe IVH in the extremely premature neonate who demonstrates persistent hypernatremia, polyuria, decreased urine osmolality, and increased plasma osmolality. Serum ADH levels can be helpful in confirming the central origin of DI and subcutaneous desmopressin can be an effective treatment in the preterm infant.

Central diabetes insipidus in pediatric patients with Langerhans cell histiocytosis: Results from the JLSG-96/02 studies.

PURPOSE: We analyzed central diabetes insipidus (CDI) development in pediatric patients with Langerhans cell histiocytosis (LCH) treated according to the Japan LCH Study Group (JLSG) regimen, which is the combination chemotherapy including cytarabine (Ara-C). METHODS: Retrospective data from 317 patients (multisystem disease (MS), n = 206; multiple focal bone (MFB), n = 111) treated according to the JLSG-96/02 regimens were analyzed. RESULTS: The median follow-up duration was 10.6 years (range, 0.1-21.1). A total of 50/317 (15.8%) patients developed CDI (MFB, n = 4; MS, n = 46). Of the 50 cases, CDI was already present at the time of LCH diagnosis (pre-CDI) in 25, and it newly developed after the diagnosis and initiation of treatment (post-CDI) in the other 25 cases. The cumulative incidence of post-CDI at 10-year calculated by Kaplan-Meier analysis was 9.0% for total and 12.0% for MS patients. A positive correlation with LCH lesions at the CNS risk sites at diagnosis was found in pre-CDI cases (17/164 vs 8/171; P = 0.0359), but not in post-CDI cases (14/129 vs 11/163; P = 0.254). Multivariate analysis showed that relapse at the CNS risk sites was significantly associated with post-CDI development (hazard ratio: 4.70; 95% CI, 1.29-17.1, P < 0.05). CONCLUSIONS: In the JLSG-96/02 studies, CDI developed in 15.8% of the cohort in which half as pre- and the other half as post-CDI. Relapse, particularly at the CNS risk sites, was linked with the development of post-CDI.

Hemorrhagic fever with renal syndrome accompanied by panhypopituitarism and central diabetes insipidus: a case report.

Central diabetes insipidus (DI) was detected in a patient with hemorrhagic fever with renal syndrome (HFRS) who had been molecularly and serologically diagnosed with Hantaan virus infection. We recommend that clinicians differentiate central DI in HFRS patients with a persistent diuretic phase even when pituitary MRI findings are normal.

'If there were water we should stop and drink': neurofibromatosis presenting with diabetes insipidus.

A 58-year-old right-handed woman presented to our institution with a 1-month history of polydipsia and polyuria. She had a remote history of neurofibroma excision by dermatology and, on examination, was noted to meet the clinical diagnostic criteria for neurofibromatosis type 1. Laboratory investigations revealed hypernatraemia and elevated serum osmolality, accompanied by reduced urinary osmolality. A subsequent water deprivation test confirmed central diabetes insipidus, which responded to treatment with desmopressin. MRI of the brain showed pituitary enlargement, which raised the possibility of an underlying pituitary adenoma or, alternatively, lymphocytic hypophysitis. Both conditions have rarely been described in neurofibromatosis.

Cardiovascular autonomic dysfunction in patients with idiopathic diabetes insipidus.

INTRODUCTION: Central diabetes insipidus (DI) is a rare disease characterized by the excretion of excessive volumes of dilute urine due to reduced levels of the antidiuretic hormone arginine vasopressin (AVP), caused by an acquired or genetic defect in the neurohypophysis. The aim of this study was to identify any autonomic dysfunction (AD) in patients with DI as a possible cofactor responsible for their reportedly higher mortality. METHODS: The study involved 12 patients (6 females) with central idiopathic DI and a well-controlled electrolyte balance, and 12 controls matched for age, sex and cardiovascular risk factors, who were assessed using the tilt, lying-to-standing, hand grip, deep breath, Valsalva maneuver and Stroop tests. RESULTS: The tilt test showed a significantly more pronounced decrease in both systolic (- 20.67 ± 18 vs. - 1.92 ± 6.99 mmHg, p = 0.0009) and diastolic blood pressure (- 10.5 ± 14.29 vs. - 1.5 ± 5 mmHg, p = 0.012) in patients than in controls. Three patients with DI had to suspend the test due to the onset of syncope. The lying-to-standing test also revealed a marked reduction in blood pressure in patients with DI (1.05 ± 0.13 vs. 1.53 ± 0.14, p = 0.0001). Similar results emerged for the Valsalva maneuver (Valsalva ratio, 1.24 ± 0.19 vs. 1.79 ± 0.11, p < 0.0001) and deep breath test (1.08 ± 0.11 vs. 1.33 ± 0.08, p < 0.0001). CONCLUSIONS: All the principal autonomic tests performed in the study were concordant in indicating that patients with central DI have an impaired autonomic nervous system function despite a normal hydroelectrolytic balance under desmopressin therapy. This impairment may reflect damage to the autonomic system per se and/or the absence of any vasoactive effect of AVP on vascular smooth muscle. In our opinion, patients with central DI should be educated on how to prevent orthostatic hypotension, and pharmacological treatment should be considered for patients with a more marked impairment.

Clinicopathological features and BRAFV600E mutations in patients with isolated hypothalamic-pituitary Langerhans cell histiocytosis.

BACKGROUND: Isolated hypothalamic-pituitary Langerhans cell histiocytosis (HPLCH) is very rare. We investigated the clinicopathological characteristics, endocrine function changes, BRAFV600E mutations and treatments of isolated HPLCH. METHODS: We identified seven patients with isolated HPLCH by reviewing the clinical and pathological files in our hospital from 2007 to 2015. The clinical characteristics of the seven patients were retrospectively reviewed, especially the endocrine function changes. Immunostaining and mutation profiling of BRAFV600E were performed. RESULTS: The seven HPLCH patients included three men and four women, aged 9-47 years. All patients presented with symptoms of central diabetes insipidus (CDI), and four displayed anterior pituitary hypofunction as well. Magnetic resonance imaging showed hypothalamic-pituitary axis involvement in all patients. There was no evidence for the involvement of other organs in all seven patients. Langerhans cell histiocytosis was confirmed by neuroendoscopic procedures, and immunohistochemical staining showed that all cases (7/7) were positive for CD68, CD1a, Langerin, and S-100. The BRAFV600E mutation was detected in three of the six cases (3/6). Six patients had follow-up information; all received desmopressin acetate and high-dose corticosteroid therapy, and two patients received radiotherapy. CONCLUSIONS: Our study indicated that all patients with isolated HPLCH had CDI as the earliest symptom, and more than half of the patients had anterior pituitary deficiencies. The BRAFV600E mutation is a common genetic change in HPLCH patients. Treatment of HPLCH patients is difficult, and the progressive loss of endocrine function is irreversible in most cases.

[Etiological diagnosis of central diabetes insipidus: about 41 cases]. / Diagnostic étiologique du diabète insipide central: à propos de 41 cas.

The occurrence of polyuria-polydipsia syndrome with hypotonic urine requires careful diagnostic strategy. This study aims to evaluate diagnostic modalities for central diabetes insipidus. We conducted a retrospective study of 41 cases with central diabetes insipidus (CDI). Data were collected at the Department of Endocrinology, University Hospital La Rabta, Tunis, from 1990 to 2013. We identified the circumstances for detecting CDI, the abnormalities in anterior pituitary assessment and pituitary imaging. CDI occurred in the postoperative period in 20 patients. The average urine 24-hour volume was significantly higher in patients with CDI outside a surgical setting. Water deprivation test was successful in all patients who benefited from it. Outside of neurosurgery, infiltration causes were found in 6 patients and tumor causes were found in 6 patients. CDI was associated with empty sella turcica in 1 case and idiopathic sella turcica in 3 patients. Hypothalamic-pituitary magnetic resonance imaging and anterior pituitary balance sheet are systematic outside pituitary surgery setting and obvious primary polydipsia.

Heterogenous patterns of recovery of thirst in adult patients with adipsic diabetes insipidus.

BACKGROUND: The natural history of adipsic diabetes insipidus (ADI) is not well described, and reports of recovery of thirst are rare. DESIGN AND METHODS: Case histories presentation. ADI was identified by demonstrating absent thirst and arginine vasopressin (AVP) responses to hypertonic saline infusion. RESULTS: Twelve patients with ADI were identified (craniopharyngioma 5, anterior communicating artery aneurysm (ACOM) repair 4, congenital 1, neurosarcoidosis 1, prolactinoma 1). Three patients died. Six patients had permanent ADI. Three patients had recovery of thirst, with a heterogenous pattern of recovery. In the first case, ADI had developed after clipping of an ACOM aneurysm. Ten years after surgery; he sensed the return of thirst; repeated hypertonic saline infusion showed recovery of thirst and AVP secretion. In the second case, a 41-year-old female with an intrasellar craniopharyngioma developed post-operative ADI with persistent hypernatremia. Two years post-operatively, she complained of thirst, and hypertonic saline infusion showed normalization of thirst but absent AVP responses, confirming recovery of thirst, but with persistent diabetes insipidus (DI). In the third case, a 29-year-old Caucasian had craniotomy and radiotherapy for craniopharyngioma and developed ADI post-operatively. Eight years post-op, she presented with thirst, seizures and pNa of 112 mmol/l. Hypertonic saline infusion showed persistent DI but thirst responses typical of compulsive water drinking; she has had recurrent hyponatraemia since then. CONCLUSIONS: We report that 3/12 patients with ADI recovered thirst after longstanding adipsia with heterogenous pattern of recovery. Both the mortality of 25% and the recovery rate of 25% should be considered when planning long-term surveillance.