Pituitary Stalk Stretch Predicts Postoperative Diabetes Insipidus After Pituitary Macroadenoma Transsphenoidal Resection.

BACKGROUND: Manipulation of the pituitary stalk, posterior pituitary gland, and hypothalamus during transsphenoidal pituitary adenoma resection can cause disruption of water electrolyte regulation leading to diabetes insipidus (DI). OBJECTIVE: To determine whether pituitary stalk stretch is an independent risk factor for postoperative DI after pituitary adenoma resection. METHODS: A retrospective review was performed of patients undergoing endoscopic endonasal resection of pituitary macroadenoma between July 2010 and December 2016 by a single neurosurgeon. We analyzed preoperative and postoperative imaging metrics to assess predictors for postoperative DI. RESULTS: Of the 234 patients undergoing resection, 41 (17.5%) developed postoperative DI. DI was permanent in 10 (4.3%) and transient in 31 (13.2%). The pituitary stalk stretch, measured as the change in stalk length from preoperative to postoperative imaging, was greater in the DI compared with the non-DI group (10.1 mm vs 5.9 mm, P < .0001). The pituitary stalk stretch was associated with DI with significant difference in mean pituitary stalk stretch between non-DI group vs DI group (5.9 mm vs 10.1 mm, P < .0001). Multivariate analysis revealed that pituitary stalk stretch >10 mm was a significant independent predictor of postoperative DI [odds ratios = 2.56 (1.10-5.96), P = .029]. When stratified into transient and permanent DI, multivariable analysis showed that pituitary stalk stretch >10 mm was a significant independent predictor of transient DI [odds ratios = 2.71 (1.0-7.1), P = .046] but not permanent DI. CONCLUSION: Postoperative pituitary stalk stretch after transsphenoidal pituitary adenoma surgery is an important factor for postoperative DI. We propose a reconstruction strategy to mitigate stalk stretch.

Masked diabetes insipidus in pituitary metastasis from breast cancer after thalamic biopsy: a case report.

BACKGROUND: Symptomatic pituitary metastasis is rare; furthermore, it can result in diabetes insipidus and panhypopituitarism. Since diabetes insipidus is masked by concurrent panhypopituitarism, it can impede the diagnosis of pituitary dysfunction. CASE PRESENTATION: A 68-year-old Japanese female suffering from pituitary and thalamic metastases caused by untreated breast cancer, underwent a biopsy targeting the thalamus, not the pituitary. She lacked prebiopsy pituitary dysfunction symptoms; however, these symptoms unexpectedly occurred after biopsy. Diabetes insipidus was masked by corticosteroid insufficiency, and she showed normal urinary output and plasma sodium levels. Upon commencement of glucocorticoid replacement therapy, the symptoms of diabetes insipidus appeared. CONCLUSIONS: In this case, thalamic biopsy, as opposed to pituitary biopsy, was performed to preserve pituitary function. However, pituitary dysfunction could not be avoided. Caution is necessary for asymptomatic patients with pituitary metastases as invasive interventions, such as surgery, may induce pituitary dysfunction. Moreover, with respect to masked diabetes insipidus, there is a need to carefully consider pituitary dysfunction to avoid misdiagnosis and delayed treatment.

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.

Preservation of Hypothalamic Function with Endoscopic Endonasal Resection of Hypothalamus-Invaded Craniopharyngiomas.

OBJECTIVE: To analyze the preservation of hypothalamic function using the endoscopic endonasal approach (EEA) in a single-center clinical series of patients with hypothalamus-invaded craniopharyngioma (CP) and compare this series with reported cases by the open transcranial approach (TCA). METHODS: A retrospective review of hypothalamus-invaded CP surgical cases treated with EEA was performed. Hypothalamic damage was evaluated in terms of the body mass index (BMI), endocrine status, and quality of life before and after surgery. A review of the available literature reporting the use of EEA and TCA over the last decade was performed for comparison. RESULTS: In total, 63 cases amenable to EEA were investigated. The elevation in BMI was substantial and an increase in BMI greater than 9% was observed in 22 patients (34.92%). Most patients exhibited a BMI gain >9% within 3 months postoperatively. A total of 16 of the 19 patients who had normal anterior pituitary function preoperatively worsened after surgery. Of the 27 cases reporting preoperative partial hypopituitarism, 16 cases worsened postoperatively and 11 cases remained unchanged. All 9 cases with preoperative panhypopituitarism remained unchanged postoperatively. A total of 40 new cases developed diabetes insipidus, and 3 of the 10 patients with preoperative diabetes insipidus exhibited resolved at the latest follow-up. The quality of life showed no significant difference. CONCLUSIONS: EEA can achieve greater gross total resection than TCA when performed by an experienced surgeon. Combined with the reduced postoperative hypothalamic damage in our patients with only hypothalamus-invaded CP, especially the shortened time horizons of hypothalamic obesity development and reduced percentage of patients with obesity, the EEA technique should be a preferred alternative over TCA.

Hyperemesis gravidarum followed by refeeding syndrome causes electrolyte abnormalities induced rhabdomyolysis and diabetes insipidus.

Although hyperemesis gravidarum (HG), an extreme form of morning sickness, is a common complication during pregnancy, HG associated simultaneous onset of rhabdomyolysis and diabetes insipidus due to electrolyte abnormalities are rare. A 34-year-old woman with severe HG at 17 weeks of gestation complicated with appetite loss, weight reduction by 17 kg, general fatigue, myalgia, weakness and polyuria was identified to have simultaneous hypophosphatemia (1.6 mg/dL) and hypokalemia (2.0 mEq/L). Appetite recovery and the improvement of the hypophosphatemia (3.2 mg/dL) were observed prior to the first visit to our department. At the admission, she presented polyuria around 7,000~8,000 mL/day with impaired concentrating activity (U-Osm 185 mOsm/L), and abnormal creatine kinase elevation (4,505 U/L). The electrolyte disturbances and physio-metabolic abnormalities in undernourished state due to HG let us diagnose this case as refeeding syndrome (RFS). In this case, abnormal loss by vomiting, insufficient intake and previous inappropriate fluid infusion as well as the development of RFS may accelerate the severity of hypokalemia due to HG. Thus, as her abnormalities were considered as results of rhabdomyolysis and diabetes insipidus due to severe HG associated hypokalemia based on RFS, oral supplementation of potassium chloride was initiated. After 6 days of potassium supplementation, her symptoms and biochemical abnormalities were completely resolved. Severe HG followed by RFS can be causes of electrolyte abnormalities and subsequent complications, including rhabdomyolysis and renal diabetes insipidus. Appropriate diagnosis and prompt interventions including adequate nutrition are necessary to prevent electrolyte imbalance induced cardiac, neuromuscular and/or renal complications.

Clinical Predictors of Diabetes Insipidus After Transcranial Surgery for Pituitary Adenoma.

OBJECTIVE: Diabetes insipidus (DI) is a well-known complication of transsphenoidal pituitary adenoma surgery. However, the risk factors for DI after transcranial surgery have not been clarified. In this study, the clinical parameters for predicting DI after transcranial surgery were investigated. METHODS: The perioperative records of 90 patients who underwent transcranial (TC) surgery at the authors' institution between November 2011 and March 2013 were chosen from 1657 patients with pituitary adenoma and retrospectively analyzed. The degree of deformation of the third ventricle and hypothalamus were assessed by preoperative magnetic resonance imaging. RESULTS: Immediate postoperative DI was found in 30 patients (33.3%). Persistent DI was noted in 11 patients (12.6%). Compared with patients in the nonpostoperative DI group, those with postoperative DI had a higher degree of deformation of the third ventricle and hypothalamus (P < 0.001). In a binary logistic regression analysis, the degree of deformation of the third ventricle and hypothalamus (odds ratio [OR], 3.079; 95% confidence interval [CI], 1.600-5.925; P = 0.001) had a significant positive correlation with immediate postoperative DI, as well as postoperative hemorrhage (OR, 6.235, 95% CI, 1.457-26.689; P = 0.014). Postoperative hemorrhage (OR, 4.363; 95% CI, 1.021-18.647; P = 0.047) showed a positive correlation with permanent DI, as well as the degree of deformation of the third ventricle and hypothalamus (OR, 2.336; 95% CI, 1.005-5.427; P = 0.049). CONCLUSIONS: The degree of deformation of the third ventricle and hypothalamus assessed by preoperative magnetic resonance imaging may help to predict postoperative DI. Postoperative hemorrhage might increase the incidence of postoperative DI, whether it is immediate postoperative DI or permanent DI.

Microsurgical anatomy of perforated arteries in the hypothalamic area.

AIM: This study aimed to investigate the microsurgical anatomy of perforating arteries in the hypothalamic area, which are associated with diabetes insipidus. MATERIAL AND METHODS: A total of 20 adult cadaver heads soaked in formalin were infused with red latex through the carotid artery and vertebral artery, and supplementary perfusion was performed after 1 day. RESULTS: The perforating arteries in the hypothalamic area could be divided into three groups according to their origins, namely, the former, below and outside groups. The former group mainly comprised the perforating arteries near the current communicating arteries. The outside group comprised the perforating arteries from the upper clinoid segment of the internal carotid and posterior communicating arteries. The below group comprised the bottom hypophyseal arteries of the cavernous segment from the internal carotid artery. CONCLUSION: Vascular injuries that occur during surgery can be minimised by understanding the distribution of the aforementioned vessels.

Expression of a dominant negative PKA mutation in the kidney elicits a diabetes insipidus phenotype.

PKA plays a critical role in water excretion through regulation of the production and action of the antidiuretic hormone arginine vasopressin (AVP). The AVP prohormone is produced in the hypothalamus, where its transcription is regulated by cAMP. Once released into the circulation, AVP stimulates antidiuresis through activation of vasopressin 2 receptors in renal principal cells. Vasopressin 2 receptor activation increases cAMP and activates PKA, which, in turn, phosphorylates aquaporin (AQP)2, triggering apical membrane accumulation, increased collecting duct permeability, and water reabsorption. We used single-minded homolog 1 (Sim1)-Cre recombinase-mediated expression of a dominant negative PKA regulatory subunit (RIαB) to disrupt kinase activity in vivo and assess the role of PKA in fluid homeostasis. RIαB expression gave rise to marked polydipsia and polyuria; however, neither hypothalamic Avp mRNA expression nor urinary AVP levels were attenuated, indicating a primary physiological effect on the kidney. RIαB mice displayed a marked deficit in urinary concentrating ability and greatly reduced levels of AQP2 and phospho-AQP2. Dehydration induced Aqp2 mRNA in the kidney of both control and RIαB-expressing mice, but AQP2 protein levels were still reduced in RIαB-expressing mutants, and mice were unable to fully concentrate their urine and conserve water. We conclude that partial PKA inhibition in the kidney leads to posttranslational effects that reduce AQP2 protein levels and interfere with apical membrane localization. These findings demonstrate a distinct physiological role for PKA signaling in both short- and long-term regulation of AQP2 and characterize a novel mouse model of diabetes insipidus.

A case of Langerhans cell histiocytosis with thyroid involvement.

Thyroid involvement with Langerhans cell histiocytosis (LCH) is very rare. We report here the case of a 15-year-old female patient with LCH affecting the thyroid gland. She was referred to the department of pediatric endocrinology for secondary amenorrhea. Prior to the diagnosis of LCH, the patient had symptoms of diabetes insipidus (DI) and amenorrhea. The mean time from symptom onset to diagnosis was 2 years. On physical examination the patient had grade 2 goiter, and ultrasound showed bilateral multiple hypoechoic nodules and thyroid heterogeneity. Biochemical analysis indicated central diabetes insipidus and panhypopituitarism. Magnetic resonance imaging (MRI) demonstrated a mass lesion involving the hypothalamus, which appeared iso- to hypo-intense on T2-weighted images and had an intense postcontrast enhancement on T1-weighted images. Nodular goiter coinciding with a hypothalamic mass suggested LCH, and an excisional biopsy was performed. Histological evaluation of the thyroid gland revealed extensive involvement by LCH, and this was confirmed by immunohistochemical analysis showing S-100 protein and CD1a positive Langerhans cells that were weakly positive for CD68. LCH should be considered in the differential diagnosis of a diffusely enlarged firm and irregular thyroid gland and posterior or anterior pituitary dysfunction.

A history of diabetes insipidus: paving the road to internal water balance.

Diabetes insipidus is an ancient disease considered under the rubric of diabetes, the Greek descriptive term for polyuria, which was unrecognized even after the sweetness of urine was reported as a characteristic of diabetes mellitus in the 17th century. It would be another century before diabetes insipidus was identified from the insipid rather than saccharine taste of urine in cases of polyuria. After its increased recognition, pathologic observations and experimental studies connected diabetes insipidus to the pituitary gland in the opening decades of the 20th century. Simultaneously, posterior pituitary lobe extracts were shown to be vasoconstrictive (vasopressin) and antidiuretic (antidiuretic hormone). As vasopressin was purified and synthesized and its assay became available, it was shown to be released in response to both osmotic and volume stimuli that are integrated in the hypothalamus, and vasopressin thereby was essential to maintaining internal water balance. The antidiuretic properties of vasopressin to treat the rare cases of diabetes insipidus were of limited clinical utility until its vasoconstrictive effects were resuscitated in the 1970s, with the consequent increasing wider use of vasopressin for the treatment of compromised hemodynamic states. In addition, the discovery of antidiuretic hormone receptor blockers has led to their increasing use in managing hypo-osmolar states.

Immediate postoperative death due to hypothalamic injury following surgery for craniopharyngioma.

Autonomic disturbances due to hypothalamic injury that result in postoperative death are rare complications following surgery for craniopharyngioma. We discuss the case of a child who died due to hypothalamic injury following radical excision of a multi-compartmental craniopharyngioma. Mechanisms and clinical manifestations of hypothalamic injury and ways to avoid this fatal complication are discussed.

[Clinical characteristics of 7 patients with gestational diabetes insipidus].

OBJECTIVE: To investigate the clinical feature, treatment and prognosis of both the mother and the fetus with gestational diabetes insipidus. METHODS: A total of 7 cases of gestational diabetes insipidus collected in the First Affiliated Hospital of Wenzhou Medical College, Wenzhou Combination of Traditional Chinese Medicine with Western Medicine Hospital, and Zhejiang Taizhou Hospital from June 1993 to June 2006 were analyzed retrospectively. RESULTS: Seven cases symptoms all characterized by excessive thirst polydipsia and polyuria. The average 24 h urinary output was between 11 L to 13 L and manifested of hypobaricuria. After effective treatment (three cases were treated with 1-deamino-8-D-arginine vasopressin, another three patients were managed with hydrochlorothiazide, and the last one was cured with antisterone), seven patients with gestational diabetes insipidus did not have any severe consequences. Their symptoms of excessive thirst, polyuria, and polydypsia disappeared from 7 days to 3 months after parturition. Urinary volume returned to normal standard of 1000-2000 ml during 24 hours. Specific gravity of urine recovered normally between a range 1.015-1.025 and serum sodium recovered between 135-147 mmol/L. The average duration of illness was 52 days. Eight newborn infants survived. Two of them were sent to neonatal intensive care unit for treatment. One was because of premature delivery caused by antepartum eclampsia, and the other case was one of the twins who had hydronephrosis. The baby of the first case left hospital after 3 weeks' treatment. The latter one's symptom disappeared 2 weeks after delivery. No obvious symptom was discovered among all the babies through follow-up telephone calls 42 days after childbirth. CONCLUSION: Gestational diabetes insipidus is a rare endocrinopathy complicating pregnancy. This disorder is characterized by excessive thirst, polydypsia, polyuria, hypobaric urine and electrolyte disturbances usually manifesting in the third trimester of pregnancy or puerperium. This is a transient syndrome. The first treatment of choice in patients with gestational diabetes insipidus is 1-deamino-8-D-arginine vasopressin and the second-choice is hydrochlorothiazide. Early diagnosis and appropriate management of the disease may reduce the hazard for both the mother and the fetus during perinatal period.

Holoprosencephaly and diabetes insipidus in a 3-month-old infant.

Holoprosencephaly is a developmental defect caused by incomplete cleavage of the embryonic forebrain structures during early embryogenesis. We describe a 3-month-old boy with median cleft palate, surgically reconstructed cleft lip, hypotelorism with a flat nose, cryptorchidism, clubfoot, and microcephaly. During the laboratory investigation, his blood sodium level was 154 mmol/L and urine specific gravity was 1.007. Serum osmolarity was 317 mOsm/kg and urine osmolarity was 268 mOsm/kg. Given these findings and the clinical response to vasopressin, diagnosis of central diabetes insipidus was made. Magnetic resonance imaging revealed semilobar holoprosencephaly. The patient responded very well to vasopressin treatment with restoration of serum electrolytes, which remained within normal limits on follow-up. In case of midline facial defects accompanied by hypotelorism with or without developmental delay, the brain should be imaged to confirm its morphology and investigations should be directed by a high index of suspicion of associated endocrinologic dysfunctions.

The effects of head trauma on hypothalamic-pituitary function in children and adolescents.

PURPOSE OF REVIEW: Endocrine dysfunctions have been increasingly recognized following traumatic brain injury. Ever more numerous studies on acute head-injured adults have also raised concern about this risk in children and adolescents who have experienced head injury. The current review of the pediatric literature summarizes recent findings on acute-phase dysfunction and traumatic brain injury-associated hypopituitarism. RECENT FINDINGS: The pathophysiologic mechanisms underlying acute-phase hyponatremic and hypernatremic disorders have been elucidated. Prospective studies on traumatic brain injury-associated hypopituitarism in pediatric patients are ongoing and preliminary data are available. SUMMARY: Traumatic brain injury, a 'silent epidemic' that carries a considerable burden of disabilities, leads to a variety of endocrine dysfunctions in 28-69% of adult acute head-injured patients. In the acute posttraumatic phase, adrenal insufficiency and electrolyte disorders are critical conditions. Neurosurgical patients, particularly those prone to neurological damage, require prompt diagnosis. Hypopituitarism may be diagnosed months or years after a traumatic brain injury event. Since growth hormone and gonadotropin secretion are most frequently compromised, careful follow-up of growth and pubertal development is mandatory in children hospitalized for traumatic brain injury.

Hypopituitarism in childhood and adolescence following traumatic brain injury: the case for prospective endocrine investigation.

Pituitary dysfunction is now well recognised after traumatic brain injury (TBI) in adults; however, little except anecdotal evidence is known about this potential complication in childhood and adolescence. Histopathological evidence exists for both hypothalamic and pituitary damage, but few data specific to children have been published. We review the available paediatric data, which shows that after both mild and severe TBI, hypopituitarism may occur, with GH and gonadotrophin deficiencies appearing to be most common. Precocious puberty has also been documented. Road-traffic accidents, falls, sport and child abuse are the most common aetiological factors for paediatric TBI. There are no published data on the incidence or prevalence, neither within a population of children with TBI, of hypopituitarism, nor on its natural history or response to hormone replacement. We urge paediatric endocrinologists, in collaboration with adult endocrinologists, to perform formal prospective research studies in patients suffering from TBI to clarify these questions.

[Hypothalamic-infundibular histiocytosis: magnetic resonance findings]. / Histiocitosis hipotálamo-infundibular: hallazgos en resonancia magnética.

INTRODUCTION: We report the magnetic resonance imaging (MRI) of a case of Langerhans cell histiocytosis in the pituitary. Isolated central nervous system involvement is uncommon. CASE REPORT: An eighteen-years old female patient who had an acute onset of central diabetes insipidus because of the Langerhans cell histiocytosis. The MRI evidenced a lesion in the hypothalamic-pituitary axis. The hyperintensity in the posterior pituitary lobe, which is seen in normal subjects on T1-weighted images, was absent. The pituitary stalk was thickened and enhanced homogeneously following contrast administration. During the follow-up, the infundibullar lesion extended to the hypothalamic region and other systemic manifestations appeared. Diagnosis of Langerhans cell histiocytosis was confirmed by lung biopsy. After radiotherapy and chemotherapy, MRI showed regression of the hypothalamic-pituitary lesion. CONCLUSION: The combination of these findings, although nonspecific of Langerhans cell histiocytosis, should nevertheless prompt further studies, including chest films, bone scanning and temporal bone computerized tomography in order to narrow the differential diagnosis.

Pancytopenia induced by hypothermia.

Hypothermia has been demonstrated to induce pancytopenia in animals, but whether this association exists in humans is unknown. The authors report the case of an 8-year-old girl in whom hypothermia (temperature 33 degrees C-35 degrees C) is the cause of pancytopenia. The patient developed thermoregulatory dysfunction subsequent to surgical resection of a craniopharyngioma. Her recurrent cytopenias could not be explained by any etiology except chronic hypothermia. The pancytopenia improved upon rewarming the patient to a temperature of 36 degrees C. This association between hypothermia and pancytopenia has rarely been reported in humans and may be underdiagnosed especially in cases of transient or milder presentations. The authors recommend careful hematologic monitoring of patients with thermoregulatory dysfunction.