Thickened pituitary stalk on magnetic resonance imaging in children with central diabetes insipidus

Magnetic resonance imaging (MRI) has revealed isolated pituitary stalk thickening (PST) in certain cases of idiopathic or secondary central diabetes insipidus (DI) due to infiltrative processes. Twenty-six children with DI and PST underwent cerebral MRI at the age of 8 +/- 4 years and were followed (n = 25) by clinical and MRI evaluation for 5.5 +/- 3.6 and 3.0 +/- 2 years, respectively, but given no treatment other than hormonal substitutive therapy. Patients were subdivided into groups according to the etiology of the DI: germinoma (n = 4), Langerhans' histiocytosis (n = 5) or 'idiopathic' DI with PST (n = 17). Complete anterior pituitary evaluation in 24 of the 26 patients revealed that 14 children were suffering from associated growth hormone deficiency and 7 had multiple hormone deficiencies. At the first MRI evaluation, pituitary stalk enlargement varied from 2.2 to 9.0 mm. The anterior pituitary gland was found to be normal (n = 12), small (n = 8) or enlarged (n = 6). At the final evaluation, a change in MRI features had occurred in 16 patients: morphological and/or signal changes in the PST (n = 16; 6 of whom showed an increase in PST) and changes in anterior pituitary gland size (n = 8; 3 of whom had increased and 5 had decreased). The presence of a growing suprasellar mass with a progressively enlarging pituitary stalk was demonstrated in the 6 patients who had shown increased pituitary stalk enlargement 1.8 +/- 1.6 years after the first MRI. In 4 of these patients, a diagnosis of germinoma was made 1.3 +/- 0.6 years after PST identification by MRI at the onset of DI, but the other 2 patients showing a suprasellar mass were still categorized as 'idiopathic' at the final clinical evaluation performed 7.8 and 12.3 years after DI onset. In 10 patients (all but 1 with Langerhans' histiocytosis, showing 'idiopathic' DI) the pituitary stalk enlargement was diminished after 2.0 +/- 1.9 years of MRI follow-up, and there was a complete reversal of pituitary stalk enlargement in 5 patients. We conclude that the natural history of 'idiopathic' isolated central DI with PST is unpredictable. Although germinoma should always be considered during the first 3 years of follow-up in patients presenting isolated DI with PST by repeated investigations every 3-6 months, it remains an infrequent etiology, affecting only 15% of cases in our study.     

Pituitary Stalk Thickening in a Large Cohort: Toward More Accurate Predictors of Pituitary Dysfunction and Etiology

Objective: To summarize the characteristics of patients with pituitary stalk thickening, analyze the association between pituitary stalk width and hypopituitarism, and develop a diagnostic model to differentiate neoplastic and inflammatory origins.Methods: A total of 325 patients with pituitary stalk thickening in a tertiary teaching hospital between January 2012 and February 2018 were enrolled. Basic characteristics and hormonal status were evaluated. Indicators to predict etiology in patients with histologic diagnoses were analyzed.Results: Of the 325 patients, 62.5% were female. Deficiency in gonadotropin was most common, followed by corticotropin, growth hormone, and thyrotropin. The increase in pituitary stalk width was associated with a risk of central diabetes insipidus (odds ratio &lsqb;OR], 3.57; P<.001) and with a combination of central diabetes insipidus and anterior pituitary deficiency (OR, 2.28; P = .029). The cut-off pituitary stalk width of 4.75 mm had a sensitivity of 69.2% and a specificity of 71.4% for the presence of central diabetes insipidus together with anterior pituitary deficiency. Six indicators (central diabetes insipidus, pattern of pituitary stalk thickening, pituitary stalk width, neutrophilic granulocyte percentage, serum sodium level, and gender) were used to develop a model having an accuracy of 95.7% to differentiate neoplastic from inflammatory causes.Conclusion: Pituitary stalk width could indicate the presence of anterior pituitary dysfunction, especially in central diabetes insipidus patients. With the use of a diagnostic model, the neoplastic and inflammatory causes of pituitary stalk thickening could be preliminarily differentiated.Abbreviations: APD = anterior pituitary dysfunction; AUC = area under the curve; CDI = central diabetes insipidus; GH = growth hormone; MRI = magnetic resonance imaging; OR = odd ratio; PHBS = posterior hypophyseal bright spots; PST = pituitary stalk thickening; PSW = pituitary stalk width     

Central diabetes insipidus as the first manifestation of neurosarcoidosis in a 10-year-old girl

Central diabetes insipidus with thickening of the pituitary stalk has been demonstrated in adults with Langerhans cell histiocytosis (LCH), tuberculosis or sarcoidosis, and in children with LCH. We present a 10.5-year-old girl with central diabetes insipidus. Magnetic resonance imaging (MRI) revealed thickening of the central part of the pituitary stalk and multiple hyperintense lesions in the frontal white matter on T(2)-weighted images. Laboratory findings were normal except for an elevated serum angiotensin-converting enzyme (ACE) level. The MRI findings together with the elevated serum ACE level highly suggest the diagnosis of sarcoidosis. We conclude that central diabetes insipidus can be the first clinical manifestation of sarcoidosis in children.     

A case of pituitary stalk tumor diagnosed with magnetic resonance (MRI)]

Authors present a case of 28-year old female with anterior hypopituitarism and diabetes insipidus, with properly functioning anterior pituitary cells as showed by means of measuring pituitary hormones in response to neurohormones i.v. injections. Magnetic resonance imaging revealed neoplastic tissue in the pituitary stalk destroying supraopticohypophysial and paraventriculohypophysial tracts, as well as portal blood system, thus preventing release of vasopressin and these hypothalamic neurohormones from accessing anterior pituitary.     

Evidence of morphological and functional abnormalities in the hypothalamus of growth-hormone-deficient children: a combined magnetic resonance imaging and endocrine study

Fifty-seven children with growth hormone deficiency and 15 healthy age-matched controls were studied by magnetic resonance imaging (MRI). Of the patients, 36 (63%) had isolated GH deficiency (IGHD) and 21 (37%) multiple pituitary hormone deficiency (MPHD). MRI studies showed a marked reduction in pituitary volume in all patients in comparison with normal controls. Moreover, a striking morphological abnormality with the apparent absence of the pituitary stalk and an ectopic posterior pituitary lobe was detected in 34 of the patients (59%). This pituitary stalk abnormality was detected in 95% of the MPHD patients and in 39% of the IGHD patients. All but one of the patients with a normal pituitary stalk had IGHD. Endocrine evaluation showed no correlation with MRI data: in particular patients with an apparent anatomical interruption of the hypothalamic-pituitary axis showed a variety of patterns of hormonal responses. In conclusion, our study shows a high frequency of hypothalamic-pituitary anomalies in patients with GH deficiency, particularly related with MPHD. However, further studies are needed to improve our understanding of the relationship between MRI and endocrine data.     

Diabetes Insipidus in Pregnancy: Etiology,Evaluation, and Management

ObjectiveTo review the approach to a patient with diabetes insipidus during pregnancy.MethodsThis review examines the normal physiology of water homeostasis, the related changes that occur during pregnancy, and the pathophysiology of diabetes insipidus in pregnancy. Associated complications, evaluation, and management are discussed.ResultsDiabetes insipidus can complicate up to 1 in 30000 pregnancies. Diabetes insipidus during pregnancy has a variety of causes, some that predate the pregnancy and others that begin during gestation. Polyuria and polydipsia can occur or be exacerbated in women with overt or subclinical central or nephrogenic diabetes insipidus. These women have either decreased central secretory reserve or impaired renal responsiveness to vasopressin. In addition, women can experience diabetes insipidus de novo in pregnancy through the actions of placental vasopressinase, which causes accelerated degradation of vasopressin. This form of diabetes insipidus may be associated with increased complications of pregnancy, including preeclampsia. Management of central diabetes insipidus and transient diabetes insipidus of pregnancy can be achieved with 1-deamino-8-D-arginine vasopressin (desmopressin acetate) (DDAVP), a vasopressin analogue. Nephrogenic diabetes insipidus is typically resistant to both DDAVP and vasopressin and underlying causes should be addressed.ConclusionsIncreased awareness of diabetes insipidus in pregnancy may lead to early diagnosis and appropriate treatment that will reduce the risks of maternal and fetal morbidity. Overall, growing experience with DDAVP has shown that it is a safe and effective treatment for diabetes insipidus caused by a variety of factors. (Endocr Pract. 2009;15:377-382)     

The Clinical Physiology of Water Metabolism: Part II: Renal Mechanisms for Urinary Concentration; Diabetes Insipidus

The renal reabsorption of water independent of solute is the result of the coordinated function of the collecting duct and the ascending limb of the loop of Henle. The unique juxtaposition of the ascending and descending portions of the loop of Henle and of the vasa recta permits the function of a counter-current multiplier system in which water is removed from the tubular lumen and reabsorbed into the circulation. The driving force for reabsorption is the osmotic gradient in the renal medulla which is dependent, in part, on chloride (followed by sodium) pumping from the thick ascending loop of Henle. Urea trapping is also thought to play an important role in the generation of a hypertonic medullary interstitium. Arginine vasopressin (AVP) acts by binding to receptors on the cell membrane and activating adenylate cyclase. This, inturn, results in the intracellular accumulation of cyclic adenosine monophosphate (AMP) which in some fashion abruptly increases the water permeability of the luminal membrane of cells in the collecting duct. As a consequence, water flows along an osmotic gradient out of the tubular lumen into the medullary interstitium.Diabetes insipidus is the clinical condition associated with either a deficiency of or a resistance to AVP. Central diabetes insipidus is due to diminished release of AVP following damage to either the neurosecretory nuclei or the pituitary stalk. Possible causes include idiopathic, familial, trauma, tumor, infection or vascular lesions. Patients present with polyuria, usually beginning over a period of a few days. The diagnosis is made by showing that urinary concentration is impaired after water restriction but that there is a good response to exogenous vasopressin therapy. Nephrogenic diabetes insipidus can be identified by a patient''s lack of response to AVP. Nephrogenic diabetes insipidus is caused by a familial defect, although milder forms can be acquired as a result of various forms of renal disease. Central diabetes insipidus is eminently responsive to replacement therapy, particularly with dDAVP, a long lasting analogue of AVP. Nephrogenic diabetes insipidus is best treated with a combination of thiazide diuretics as well as a diet low in sodium and protein.     

Superiority of magnetic resonance imaging (MRI) over computerized tomography (CT) in diagnosis of hypopituitarism]

Hypopituitarism can be a result of various lesions of hypothalamus, pituitary stalk, or of the pituitary gland itself. The aim of the study was to assess the value of CT and MRI examinations in determination of the cause of hypopituitarism. Seventeen patients with hypopituitarism (9 women and 8 men) aged 22 to 61 years have been examined. In three cases growth deficiency was observed, 4 women had galactorrhoea, 4 patients had diabetes insipidus, 16 patients had supra-adrenal insufficiency, 14 had signs of hypogonadism and 10 hypothyroidism. In each case plasma concentrations of LH, FSH, PRL, TSH, alpha-subunit, ACTH before and after appropriate stimulation with TRH, metoclopramid, LH-RH, GRF or metyrapon were determined with RIA. Every patient was examined both with CT and MRI (0.5 T Toshiba MRT 50a). All 17 patients had abnormal MR images of hypothalamo-pituitary area, while only 10 of them had abnormalities in their CT scans. In remaining 7 patients the MRI revealed: three cases of congenital malformation of hypophyseal stalk, two cases of empty sella, one posttraumatic lesion of the stalk and one case of granulomatous infiltration of the stalk. We found MRI superior to CT in establishing the case of hypopituitarism.     

Metastatic Burkitt's Lymphoma Presenting as Diabetes Insipidus

ObjectiveTo present the first reported case of metastatic Burkitt's lymphoma with a single central nervous system (CNS) metastasis to the pituitary stalk.MethodsWe provided details of the case presentation and review the literature.ResultsAlthough other malignancies are known to metastasize to the pituitary, and diabetes insipidus is often the presenting symptom, there has not been a previously reported case of Burkitt's lymphoma with a single CNS metastasis to the pituitary.ConclusionA careful history and an endocrine review of systems may aid early identification of pituitary or central nervous system metastases. (Endocr. Pract. 2013; 19:e102-e104)     

Radiation-induced growth hormone deficiency

Deficiency of one or more anterior pituitary hormones may follow treatment with external irradiation when the hypothalamic-pituitary axis falls within the fields of irradiation. Hypopituitarism occurs in patients who receive radiation therapy for pituitary tumours, nasopharyngeal cancer and primary brain tumours, as well as in children who undergo prophylactic cranial irradiation for acute lymphoblastic leukaemia, or total body irradiation for a variety of tumours and other diseases. The degree of pituitary hormonal deficit is related to the radiation dose received by the hypothalamic-pituitary axis. Thus, after lower radiation doses isolated growth hormone deficiency ensues, whilst higher doses may produce hypopituitarism. The timing of onset of the radiation-induced pituitary hormone deficit is also dose-dependent. The main site of radiation damage is the hypothalamus rather than the pituitary, although the latter may be affected directly.     

Diabetes Insipidus,Panhypopituitarism, and Severe Mental Status Deterioration in a Patient with Chordoid Glioma: Case Report and Literature Review

ObjectiveTo describe a rare progressive case of chordoid glioma clinically masquerading as idiopathic diabetes insipidus (DI).MethodsWe describe the clinical, radiographic, and laboratory findings of the study patient and briefly review the relevant literature.ResultsA 41-year-old woman was referred to our center for evaluation of worsening mental status changes, a newly diagnosed suprasellar mass, and possible endocrine dysfunction. Three years earlier, a physician at another institution diagnosed idiopathic DI and prescribed desmopressin. At that time, laboratory workup and magnetic resonance imaging (MRI) revealed no brain lesions or other hormonal irregularities. Slow, progressive symptomatology in the following 3 years included mental status changes, nonhealing skin lesions, recurrent infections, temperature dysregulation, and midsection weight gain. She became withdrawn and emotionally labile and developed a flat affect, short-term memory loss, poor concentration, and sleep disturbance. MRI revealed a 2.2 × 2.1 × 1.9-cm suprasellar region lesion. Biopsy samples from the third ventricular lesion revealed a circumscribed glial tumor. Chordoid glioma is a rare tumor, and the 50 previously reported cases have been located in the suprasellar region. This is the third reported case of a chordoid glioma positive for neurofilament protein, which brings into question the hypothesis of a single phenotype for glial tumors. Tumors in this region frequently result in endocrine dysfunction that prompts patients to seek medical attention.ConclusionsThere is no formally recognized treatment protocol for chordoid glioma, and postoperative mortality and morbidity is high. Our report emphasizes the necessity of close follow-up of patients after a diagnosis of idiopathic DI. Early detection of any evolving occult hypothalamic-pituitary stalk lesion may improve outcome. (Endocr Pract. 2009;15:240-245)     

Xanthoma Disseminatum: Case Report and Literature Review

ObjectiveTo report a case of a young normolipidemic woman with mucocutaneous xanthomas who developed neurogenic diabetes insipidus and hyperprolactinemia because of an inflammatory pituitary stalk lesion.MethodsThe clinical features, laboratory results, magnetic resonance imaging, and pathology findings are presented. In addition, the pertinent literature is reviewed.ResultsA 23-year-old woman presented with a 9-month history of polydipsia, polyuria, galactorrhea, secondary amenorrhea, and weight gain. Her previous medical history included chronic anemia and widespread mucocutaneous xanthomas. Laboratory tests showed hyperprolactinemia, normal electrolytes, and a normal lipid profile. The results of a water deprivation test were compatible with neurogenic diabetes insipidus, and cerebral magnetic resonance imaging showed pituitary stalk thickening. Histologic findings on a skin biopsy specimen supported the diagnosis of non-Langerhans histiocytosis. Treatment was initiated with cabergoline, nasally administered desmopressin, radio-frequency ablation of facial skin lesions, and surgical excision of other accessible lesions.ConclusionXanthoma disseminatum is a rare, benign proliferative disorder characterized by extensive cutaneous and mucous membrane xanthomas in normolipidemic patients. Central nervous system involvement is rare and usually occurs in the systemic variety. Pituitary stalk disease commonly causes hyperprolactinemia, diabetes insipidus, and various degrees of hypopituitarism. The natural history of xanthoma disseminatum usually is benign, but lesions in critical anatomic sites may result in morbidity and mortality. (Endocr Pract. 2010;16:1003-1006)     

Guía clínica de manejo de la diabetes insípida y del síndrome de secreción inapropiada de hormona antidiurética en el postoperatorio de la cirugía hipofisaria

Changes in water metabolism and regulation of vasopressin (AVP) or antidiuretic hormone (ADH) are common complications of pituitary surgery. The scarcity of studies comparing different treatment and monitoring strategies for these disorders and the lack of prior clinical guidelines makes it difficult to provide recommendations following a methodology based on grades of evidence. This study reviews the pathophysiology of diabetes insipidus and inappropriate ADH secretion after pituitary surgery, and is intended to serve as a guide for their diagnosis, differential diagnosis, treatment, and monitoring.     

Eventos adversos perinatales y anomalías neuroanatómicas en pacientes con hipopituitarismo idiopático

ObjectiveTo analyze the possible causes of growth hormone (GH) deficiency, whether isolated (GHD) or in combination with other pituitary deficiencies classified as idiopathic.Patients and methodsWe studied patients with idiopathic GHD included in a protocol of recombinant GH treatment in adults attending the outpatient clinic of the Endocrinology and Nutrition Service of the San Cecilio University Hospital. Perinatal history, findings on magnetic resonance imaging (MRI) of the hypothalamic-pituitary axis and diagnosis of GHD and other deficiencies were retrospectively evaluated.ResultsA total of 17 patients were included: 14 men and 3 women with a mean age at diagnosis of 8.4±7.3 years. Perinatal adverse events occurred in 12 patients (69.2%). MRI showed empty sella (2 patients), pituitary hypoplasia or absence of the pituitary stalk (7 patients) and pituitary hypoplasia with ectopic posterior pituitary gland (6 patients); in the remaining 2 patients these data were not available. All had an established diagnosis of GHD: 15 with (88.2%) gonadotropin deficiency, 9 (52.9%) with adrenocorticotropic hormone (ACTH) deficiency and 8 (47.1%) with thyroid-stimulating hormone (TSH) deficiency.ConclusionsIn our patients, adverse events during pregnancy or the perinatal period and the presence of anatomical abnormalities identified by MRI are a marker of pituitary dysfunction and may be important in the pathogenesis of this entity. The clinical spectrum of disease varies from isolated GH deficiency to multiple pituitary hormone deficiencies.     

Vasopressin deficiency decreases the frequency of gastroduodenal ulceration in humans.

Vasopressin is a stress hormone released from the posterior pituitary. In humans suffering from central diabetes insipidus, this release of vasopressin is diminished. It was shown previously that the congenitally vasopressin-deficient Brattleboro homozygous rat is less sensitive to various ulcerogenic stimuli. In this study, we investigated the incidence of gastroduodenal ulceration in vasopressin deficient patients. Data on patients aged 20-70, hospitalized in Hungary between 1992 and 1995 were compared with those on the total population in this age group (6,681,020 in 1994). Subjects with central diabetes insipidus were selected separately (815 cases). Gastroduodenal ulceration was compared in subjects with an intact vasopressin release and vasopressin-deficient patients. The frequencies of gastroduodenal ulceration were also examined separately in male and female subjects. In the total population, the frequency of gastroduodenal ulceration was lower in vasopressin-deficient cases (2.22% versus 0.61%; P < 0.005). Among normal-vasopressin subjects, males have a higher risk of gastroduodenal ulceration than females (3.04% versus 1.46%, respectively; P < 0.001). Among vasopressin-deficient subjects, a similar male:female ratio was observed, but it was not significant (P = 0.36). In comparison to the normal-vasopressin population, the incidence of gastroduodenal ulceration was reduced among vasopressin-deficient males and females by 77% (P < 0.01) and by 82% (P < 0.05), respectively. In conclusion, endogenous vasopressin has a significant harmful action towards the human gastroduodenal mucosa. Peptide and non-peptide vasopressin receptor antagonists might have a potential therapeutic benefit in the treatment (as an adjuvant) and prevention of gastroduodenal ulceration.     

Hypopituitarism and stalk agenesis: a congenital syndrome worsened by breech delivery?

Thirty-seven patients with idiopathic hypopituitarism, of whom 12 had multiple pituitary hormone deficiencies (MPHD) and 25 isolated growth hormone deficiency (IGHD), were evaluated by magnetic resonance imaging (MRI). Twenty-two of the 37 showed congenital anterior pituitary hypoplasia, stalk agenesis and ectopic posterior pituitary gland at the infundibular recess (group A), while the remaining 15 presented isolated anterior pituitary hypoplasia (group B). Perinatal histories obtained from all patients demonstrated that 18/22 children of group A (81.81%) had histories of adverse perinatal events, with breech presentation in 15 (68.18%). Twelve of 12 children of group A born by breech delivery developed MPHD; 3 born by cesarean section for breech presentation had only IGHD. Patients of group B had also a high incidence of perinatal insults (12/15, 80%), but breech delivery was markedly less frequent (13.33 vs. 68.18% of group A) and responsible for only IGHD. Group B had also higher percentages of maternal spontaneous abortion and low birth weight. Our study suggests that several factors may play a role in the development of growth hormone deficiency. Some patients had severe perinatal insults apparently leading to hypopituitarism. We were able to define by MRI a group of patients with congenital abnormalities, such as anterior pituitary hypoplasia, stalk agenesis and posterior pituitary ectopia, among whom breech presentation was very common. In this group, breech delivery was always followed by MPHD while cesarean or normal delivery in such patients was followed by IGHD only.     

Hypothalamic Germinoma Masquerading as Superior Mesenteric Artery (Sma) Syndrome

ObjectiveTo report a case of superior mesenteric artery (SMA) syndrome secondary to hypothalamic germinoma.MethodsWe describe the clinical presentation, diagnostic work-up, management, and clinical course of a patient admitted with SMA syndrome who was subsequently found to have a hypothalamic germinoma.ResultsAn adolescent boy was admitted to the surgical ward with progressive weight loss over a 2 year period and postprandial vomiting. He was diagnosed with SMA syndrome based on evidence of proximal duodenal dilatation, extrinsic compression of the distal duodenum, and a narrowed aortomesenteric angle (16°). Investigations performed to exclude thyrotoxicosis unexpectedly revealed secondary hypothyroidism and further evaluation demonstrated evidence of pan-hypopituitarism. Psychiatric evaluation excluded anorexia nervosa and bulimia. Magnetic resonance imaging (MRI) of the brain revealed a heterogeneously enhancing hypothalamic lesion, but a normal pituitary gland. Hormone replacement with hydrocortisone, desmopressin, testosterone, and thyroxine resulted in weight gain and resolution of gastrointestinal symptoms. A transventricular endoscopic biopsy subsequently confirmed a hypothalamic germinoma and he was referred to an oncologist.ConclusionSMA syndrome secondary to severe weight loss is an uncommon cause of upper gastrointestinal obstruction. While there have been reports of poorly controlled diabetes mellitus and thyrotoxicosis manifesting as SMA syndrome, there are no published reports to date of SMA syndrome secondary to hypothalamic/pituitary disease. Management of SMA syndrome is conservative, as symptoms of intestinal obstruction resolve with weight gain following treatment of the underlying cause. Awareness of this uncommon presentation of endocrine cachexia/hypothalamic disease will prevent unnecessary laparotomies and a misdiagnosis of an eating disorder. (Endocr Pract. 2013;19:e29-e34)     

The Emerging Role of Copeptin

Direct measurement of the nonapeptide vasopressin has been limited by analyte instability ex vivo and in vivo rapid degradation, low serum concentrations requiring a sensitive assay and inherent secretory pulsatility. Copeptin is a 39 amino acid glycopeptide cleavage product of vasopressin synthesis with high stability, providing a marker of vasopressin secretion. Copeptin measurement has applications in diagnosis of diabetes insipidus and other diseases with altered vasopressin secretion. This review summarises our current understanding of serum copeptin measurement in diabetes insipidus and possible future applications of copeptin assays. As vasopressin is a stress hormone, there is emerging evidence on the use of copeptin for diagnosis and prognostication of disorders such as syndrome of inappropriate anti-diuretic hormone secretion, diabetes mellitus, critical illness, stroke, cardiovascular disease, respiratory disease, renal disease and thermal stress. Copeptin concentration measurement is likely to improve the diagnostic reliability of diabetes insipidus and, as a marker of stress, may have diagnostic or prognostic utility in specific clinical circumstances. Further studies are needed to determine if goal-directed therapy using plasma copeptin concentrations may improve patient outcomes.