Case Report: SARS-CoV-2 Infection in a Child With Suprasellar Tumor and Hypothalamic-Pituitary Failure.

In early 2020, a novel coronavirus leading to potentially death was discovered. Since then, the 2019 coronavirus disease (COVID-19) has spread to become a worldwide pandemic. Beyond the risks strictly related to the infection, concerns have been expressed for the endocrinological impact that COVID-19 may have, especially in vulnerable individuals with pre-existing endocrinological health conditions. To date new information is emerging regarding severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in children but the literature is still scarce concerning this infection in patients with intracranial malignant neoplasms. We report a 9-year-old child infected with SARS-CoV-2 and recent diagnosis of suprasellar non-germinomatous germ cell tumor also suffering from diabetes insipidus and hypothalamic-pituitary failure (hypothyroidism, adrenal insufficiency, hypothalamic obesity and growth hormone deficiency) and its clinical course. The patient remained asymptomatic for the duration of the infection without requiring any change in the replacement therapeutic dosages taken before the infection. We then discuss the proposed approach to treat a pediatric patient with SARS-CoV-2 infection and hypothalamic-pituitary failure and we include a review of the literature. Our report suggests that SARS-CoV-2 infection is usually mild and self-limiting in children even those immunocompromised and with multiple endocrinological deficits. Patients are advised to keep any scheduled appointments unless informed otherwise.

Viral rescue of magnocellular vasopressin cells in adolescent Brattleboro rats ameliorates diabetes insipidus, but not the hypoaroused phenotype.

Dysregulated arousal often accompanies neurodevelopmental disorders such as attention deficit hyperactivity disorder and autism spectrum disorder. Recently, we have found that adolescent homozygous Brattleboro (Hom) rats, which contain a mutation in the arginine vasopressin (AVP) gene, exhibit lower behavioral arousal than their heterozygous (Het) littermates in the open field test. This hypoaroused phenotype could be due to loss of AVP in magnocellular cells that supply AVP to the peripheral circulation and project to limbic structures or parvocellular cells that regulate the stress axis and other central targets. Alternatively, hypoarousal could be a side effect of diabetes insipidus - polydipsia and polyuria seen in Hom rats due to loss of AVP facilitation of water reabsorption in the kidney. We developed a viral-rescue approach to "cure" magnocellular AVP cells of their Brattleboro mutation. Infusion of a recombinant adeno-associated virus (rAAV) containing a functional Avp gene and promoter (rAAV-AVP) rescued AVP within magnocellular cells and fiber projections of the paraventricular nucleus of the hypothalamus (PVN) of male and female adolescent Hom rats. Furthermore, water intake was markedly reduced, ameliorating the symptoms of diabetes insipidus. In contrast, open field activity was unaffected. These findings indicate that the hyporaoused phenotype of adolescent Hom rats is not due to the loss of AVP function in magnocellular cells or a side effect of diabetes insipidus, but favors the hypothesis that central, parvocellular AVP mechanisms underlie the regulation of arousal during adolescence.

Oxytocin alterations and neurocognitive domains in patients with hypopituitarism.

PURPOSE: Oxytocin is a hypothalamus derived, posterior pituitary stored nonapeptide which has gained recent interest as an important neuropsychiatric and metabolic hormone beyond its classic role in lactation and parturition. Hypopituitarism is a heterogenous disorder of derangement in one or more anterior or posterior pituitary hormones. Diagnosis of deficiency and hormone replacement exists to address all relevant axes except for oxytocin. Our study aims to define derangements in oxytocin in a unique population of patients with hypopituitarism and correlate levels with measures of emotional health and quality of life. METHODS: A cross-sectional, single day study was completed to measure plasma oxytocin levels in a diverse population of patients with hypopituitarism compared to controls. Subjects also completed depression, quality of life and stress-related questionnaires, and emotion recognition tasks. RESULTS: Thirty-eight subjects completed the study, 18 with hypopituitarism (9 with diabetes insipidus) and 20 controls. After controlling for differences in age, weight and gender, plasma oxytocin levels were highest in subjects with diabetes insipidus compared to control [mean, IQR: 44.3 pg/ml (29.8-78.2) vs. 20.6 (17-31.3), p = 0.032]. Amongst hypopituitary subjects, those with duration of disease greater than 1 year had higher oxytocin levels. No significant differences were observed for psychosocial measures including emotion recognition tasks. CONCLUSIONS: Plasma oxytocin levels were found higher in patients with hypopituitarism compared to controls and highest in those with diabetes insipidus. Longer duration of hypopituitarism was also associated with higher plasma levels of oxytocin. Further study is needed to better define oxytocin deficiency and investigate response to treatment.

Outcomes of endoscopic and microscopic transsphenoidal surgery on non-functioning pituitary adenomas: a systematic review and meta-analysis.

Both microscopic and endoscopic transsphenoidal surgery are effective approaches for nonfunctioning pituitary adenomas. The issue on the comparison of their efficacy and safety remains inconsistent. A thorough search of the literatures (PubMed, EMBASE, MEDLINE) were performed up to March 2017. Studies reporting outcomes of microscopic or endoscopic transsphenoidal surgery on nonfunctioning pituitary adenomas were included. A meta-analysis was performed focusing on the early stage and long term outcomes. The final search yielded 19 eligible studies enrolling 3847 patients, 389 of them underwent microscopic approach and 3458 of them with endoscopic approach. As to the early stage outcomes, the rate of gross tumor resection was significantly higher in the endoscopic group than that in microscopic group (73% versus 60%, P < 0.001). Meanwhile, endoscopic approach showed priority over microscopy on postoperative hypopituitarism (63% versus 65%, P < 0.001) and CSF leakage (3% versus 7%, P < 0.001). For the long term outcomes, the rate of visual improvement was significant higher in the endoscopic group than that in microscopic group (77% versus 50%, P < 0.001). However, there was no significant difference between the groups regarding the rate of permanent diabetic insipidus and meningitis. The endoscopic approach may be associated with higher rate of gross tumor movement and lower risk of postoperatively complications for treating nonfunctioning pituitary adenoma, when compared with microscopic approach. However, the confidence was shorted due to limited high quality evidence (largely randomized and controlled studies).

Long-Standing Isolated Autoimmune Hypothalamitis Diagnosed with Endoscopic Transventricular Biopsy.

BACKGROUND: Autoimmune hypothalamitis, which is among the causes of acquired central diabetes insipidus, has seldom been described in the literature. This condition is probably provoked by the production of anti-vasopressin-secreting cell antibodies and antihypothalamus antibodies and is often associated with pituitary or polyendocrine autoimmunity. Correct diagnosis and immediate treatment are essential to avoid the progression of the pathologic process. CASE DESCRIPTION: A woman diagnosed with central diabetes insipidus 12 years ago, who had panhypopituitarism and mild memory deficit, came to our attention. She refused radiologic studies. Magnetic resonance imaging performed in our unit showed a contrast-enhancing hypothalamic lesion. Lumbar puncture was negative for neoplastic markers. We decided to perform a biopsy of the lesion to obtain a histopathologic examination of the tissue and chose an endoscopic transventricular approach to reach the floor of the third ventricle. Autoimmune hypothalamitis was diagnosed and treatment with steroids and azathioprine was started. The lesion size decreased and was stable after 17 months of follow-up. CONCLUSIONS: The endoscopic transventricular approach has proved to be an effective and safe way to obtain tissue samples for histopathologic examination from a region that is usually difficult to reach; it also gives direct visualization of the lesion, which makes sampling easier. The lesion size decreased after treatment but no clinical improvement was detected, either on the cognitive or on the endocrinologic side.

Renal compensatory adaptation for water handling in a patient with adipsic diabetes insipidus after clipping of a ruptured aneurysm of the anterior communicating artery
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A 38-year-old Japanese man who had undergone clipping surgery for a ruptured aneurysm of the anterior communicating artery 2 days prior, suddenly developed refractory hypernatremia (serum sodium (Na) 156 - 162 mmol/L). Symptoms included low plasma vasopressin, fluctuating urine osmolality (120 - 710 mOsm/kg) and lack of thirst, all suggesting adipsic diabetes insipidus (ADI). Hypernatremia was corrected by scheduled water intake with desmopressin administration. During 1-year follow-up after the surgery, his serum Na level normalized despite the suspension of desmopressin, but neither thirst nor osmolality-dependent vasopressin release recovered. Meanwhile, his urine osmolality shifted to a constant high level. The present case suggests that renal compensatory adaptation, apparently independent of the circulating vasopressin level, plays a major role in water handling in longitudinal ADI.
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Prospective study of hypothalamo-hypophyseal dysfunction in children and adolescents following traumatic brain injury.

BACKGROUND AND AIMS: Retrospective studies of TBI have found a neuroendocrine dysfunction following traumatic brain injury in 23 to 60% of adults and 15 to 21% of children. Our aims were to determine the prevalence of hypothalamo-hypophyseal dysfunction in children following brain injury, assess its relationship to the type of injury and the course of the acute post-traumatic phase. PATIENTS AND METHODS: Body development (growth, pubertal development, and skeletal maturity) were evaluated in 58 patients (21 girls) after a brain injury rated 3 to 12 on the Glasgow Coma Scale (GCS). The patients underwent standard endocrine tests - TSH, fT4, IGF-1, PRL, morning cortisol, FSH, LH, and testosterone in boys and estradiol in girls - in the early post-traumatic period (2 to 14 days; T0) and at 3, 6, and 12 months after the injury (T3, T6, and T12). Dynamic tests were carried out in patients with abnormalities in their clinical examination and/or laboratory results. An MRI was performed on all patients at T12. RESULTS: The median age at the time of injury was 11.3 (0.5 to 18.7) years. Of the 58 patients, 23 had GCS < 8, corresponding to severe brain injury. At T0, diabetes insipidus (DI) was diagnosed in 12 patients, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was found in 4 patients. Frequent hormonal changes simulated central hypothyroidism (in 45% of patients) and hypogonadotropic hypogonadism (in 25% of adolescents who were already pubertal at the time of injury > Tanner II). Examination at T3 (n = 58) confirmed a combined pituitary hormone deficiency in two boys and DI in another one. At T6 (n = 49), hormonal dysfunctions were diagnosed in two boys (precocious puberty and growth hormone deficiency). At T12 (n = 39), a new endocrine dysfunction was diagnosed in five patients (growth hormone deficiency in two, hypogonadotropic hypogonadism in two, and in one patient, already diagnosed with a growth hormone deficiency, central hypothyroidism, as well). Brain MRI revealed an empty sella in two patients with growth hormone deficiency. Patients with GCS < 8 had more symptoms of SIADH or DI in the early post-traumatic period 11/23 vs. patients with GCS of 8 to 13 (4/35), and more frequent hormonal disorder (6/23) than individuals with moderate trauma (3/35), P = 0.0135. The incidence of endocrine dysfunction at T0 significantly correlated with the severity of injury (P = 0.05), but it was not an indicator for the development of a late hormonal disorder. CONCLUSION: Within a year after injury, a hormonal disorder was found in 17.6% of the patients. Neuroendocrine dysfunction as a late consequence of craniocerebral trauma in children and adolescents was less frequent than in adults. Risk factors for its development are the gravity of the injury, brain scan pathology, and possibly the development of DI, SIADH, or CSWS in the acute post-traumatic phase.

Endocrine changes in histiocytosis of the hypothalamic-pituitary axis.

Histiocytosis is characterized by proliferation of cells from the mononuclear phagocyte system, and may be divided into Langerhans cell histiocytosis (LCH) and non-Langerhans cell histiocytosis (including Erdheim-Chester disease [ECD]). While diabetes insipidus (DI) is the most common hypothalamic-pituitary consequence, anterior pituitary deficiencies are less known. This study analyzed the frequency and progression of pituitary hormone deficiencies and the radiographic findings in 9 patients (7 with LCH and 2 with ECD) with hypothalamic-pituitary (HP) axis. Eighty-nine percent of patients had DI (62% at diagnosis), and 78% had one or more anterior pituitary deficiencies (71% at diagnosis). HP involvement is relatively common in patients diagnosed with histiocytosis and hormone deficiencies may be present at diagnosis or appear gradually during the course of disease. Regular monitoring of these patients is recommended.

A novel method for managing water and electrolyte balance after transsphenoidal surgery: preliminary study of moderate water intake restriction.

Hyponatremia is a common and potentially serious complication of transsphenoidal surgery (TSS). Since September 2009, we have implemented moderate water intake restriction (< 2500 mL/day) after TSS in an attempt to prevent this complication. The aim of this study was to investigate the efficacy of a combination of moderate restriction of water intake plus antidiuretic hormone (arginine vasopressin [AVP]) replacement therapy in patients with diabetes insipidus (DI) for reducing the incidence of delayed hyponatremia after TSS. Patients treated from September 2005 to August 2009 were allowed to drink water freely after surgery (the control group), while patients treated from September 2009 to June 2012 were restricted to less than 2500 mL water per day (the water restriction group). To reduce the occurrence of hypernatremia, AVP replacement therapy was provided immediately after the development of DI. We retrospectively analyzed the incidence of hyponatremia, DI, and hypernatremia in patients following TSS. Hyponatremia incidence was significantly lower in the water restriction group (P = 0.017); however, there were no significant differences in DI incidence and hypernatremia incidence between the 2 groups. Under DI control with AVP replacement therapy, the water restriction group showed no significant difference in the daily self-rated thirst level for the patients with and without DI. Moderate water intake restriction in addition to AVP replacement therapy significantly decreases the incidence of hyponatremia without patient discomfort (extreme thirst) and other complications. However, further studies are required to determine the most effective amount of water and the optimal duration of postoperative water restriction.

[Hormonal dysnatremia]. / Les dysnatrémies hormonales.

Because of antidiuretic hormone (ADH) disorder on production or function we can observe dysnatremia. In the absence of production by posterior pituitary, central diabetes insipidus (DI) occurs with hypernatremia. There are hereditary autosomal dominant, autosomal recessive or X- linked forms. When ADH is secreted but there is an alteration on his receptor AVPR2, it is a nephrogenic diabetes insipidus in acquired or hereditary form. We can make difference on AVP levels and/or on desmopressine response which is negative in nephrogenic forms. Hyponatremia occurs when there is an excess of ADH production: it is a euvolemic hypoosmolar hyponatremia. The most frequent etiology is SIADH (syndrome of inappropriate secretion of ADH), a diagnostic of exclusion which is made after eliminating corticotropin deficiency and hypothyroidism. In case of brain injury the differential diagnosis of cerebral salt wasting (CSW) syndrome has to be discussed, because its treatment is perfusion of isotonic saline whereas in SIADH, the treatment consists in administration of hypertonic saline if hyponatremia is acute and/or severe. If not, fluid restriction demeclocycline or vaptans (antagonists of V2 receptors) can be used in some European countries. Four types of SIADH exist; 10 % of cases represent not SIADH but SIAD (syndrome of inappropriate antidiuresis) due to a constitutive activation of vasopressin receptor that produces water excess. c 2013 Published by Elsevier Masson SAS.

An unusual case of central diabetes insipidus & hyperglycemic hyperosmolar state following cardiorespiratory arrest.

BACKGROUND: We are describing an unusual case of severe hyperglycemia and hypernatremia, resistant to treatment. CASE PRESENTATION: A thirty year old female with adenocarcinoma of rectum was admitted with increasing lethargy, headache and drowsiness. She deteriorated rapidly and had cardiac arrest, following which she remained comatose. Her initial serum glucose and sodium were normal, but after receiving dexamethasone and mannitol, the serum glucose progressively increased to 54.7 mmol/L and sodium to 175 mmol/L, despite receiving very high dose of intravenous (IV) insulin infusion. She was evaluated for diabetes insipidus because of continued polyuria even after correction of hyperglycemia. Her serum osmolality was 337 mmol/kg, and urine osmolality was 141 mmol/kg which rose to 382 mmol/kg, after receiving 4 mcg of IV Desmopressin. CONCLUSION: Our patient developed central diabetes insipidus post cardiac arrest and severe dehydration because of diabetes insipidus. Stress of critical illness, dehydration, dexamethasone and IV dextrose infusion were likely responsible for this degree of severe and resistant to treatment hyperglycemia.

Temporary diabetes insipidus in 2 men after on-pump coronary artery bypass grafting.

Many complications have been reported after cardiopulmonary bypass. A common physiologic change during the early postoperative period after cardiopulmonary bypass is increased diuresis. In patients whose urine output is increased, postoperative diabetes insipidus can develop, although reports of this are rare. We present the cases of 2 patients who underwent on-pump coronary artery bypass grafting (with cardiopulmonary bypass). Each was diagnosed with diabetes insipidus postoperatively: a 54-year-old man on the 3rd day, and a 66-year-old man on the 4th day. Each patient recovered from the condition after 6 hours of intranasal therapy with synthetic vasopressin (antidiuretic hormone). The diagnosis of diabetes insipidus should be considered in patients who produce excessive urine early after cardiac surgery in which cardiopulmonary bypass has been used.

Pituitary stalk lesions: the Mayo Clinic experience.

CONTEXT: Pituitary stalk lesions have various etiologies, often not clinically apparent. Pathological samples from these lesions are rarely obtained, because of the critical location and function of the hypophyseal stalk. OBJECTIVES: The purpose of this study was to characterize the etiological spectrum of pituitary stalk lesions seen at Mayo Clinic Rochester over 20 years and to determine whether specific magnetic resonance imaging (MRI) characteristics could provide clinician guidance with regard to the etiology of infundibular lesions. DESIGN: A retrospective review of patients with pituitary stalk lesions seen at Mayo Clinic Rochester between 1987 and 2006 was conducted. Demographic, clinical presentation, imaging, laboratory, operative, and pathology data were reviewed and are reported using descriptive statistics. RESULTS: Of the 152 pituitary stalk lesions included, 49 (32%) were neoplastic, 30 (20%) were inflammatory, 13 (9%) were congenital anomalies, and 60 (39%) were of unclear etiology. Diabetes insipidus was diagnosed in 43 (28%) of the 152 patients, and 49 (32%) patients had at least one anterior pituitary hormone deficit. Secondary hypogonadism was the most common endocrine deficiency. Eleven of 13 congenital lesions were round in appearance and 5 of 7 patients with neurosarcoidosis confirmed by pathology had a uniformly thickened pituitary stalk on MRI. There were no statistically significant correlations between hypopituitarism and the pattern of enhancement or size of the lesion. CONCLUSIONS: Findings on MRI remain key in guiding the diagnosis of pituitary stalk lesions, particularly when used in conjunction with other clinical clues. There are no good imaging predictors for hypopituitarism, making clinical evaluation of all patients with pituitary stalk lesions crucial.

Managing the patient with transsphenoidal pituitary tumor resection.

Patients who undergo transsphenoidal pituitary tumor resection require a multidisciplinary team approach, consisting of a neurosurgeon, an endocrinologist, and nurses. Successful transsphenoidal surgery needs expert nursing care for early identification and prompt treatment of pituitary dysfunction and neurosurgical complications. Pituitary dysfunction includes adrenal insufficiency, diabetes insipidus, syndrome of inappropriate antidiuretic hormone, and cerebral salt wasting syndrome. Neurosurgical complications may include visual disturbance, cerebrospinal fluid leak, subdural hematoma, and epistaxis.

A case of thymic Langerhans cell histiocytosis with diabetes insipidus as the first presentation.

Langerhans cell histiocytosis (LCH) is an idiopathic group of reactive proliferative diseases linked to aberrant immunity, pathologically characterized by clonal proliferation of Langerhans cells. LCH rarely involves the thymus. We report a case of thymic LCH with diabetes insipidus as the first presentation, without evidence of myasthenia gravis and without evidenced involvement of the skin, liver, spleen, bones, lungs and superficial lymph nodes. This present case may have important clinical implications. In screening for LCH lesions, attention should be attached to rarely involved sites in addition to commonly involved organs. Follow-up and imageological examination are very important to a final diagnosis.

Cushing's disease presenting with pituitary apoplexy.

Pituitary tumour apoplexy is a rare but life threatening condition. Cushing's disease usually presents with clinical features of Cushing's syndrome. We report a 30-year-old male patient with Cushing's disease who presented with severe headache and right third nerve palsy. MRI of the pituitary gland revealed a pituitary adenoma with infarction suggestive of apoplexy. After a transsphenoidal surgery he developed pan-hypopituitarism with diabetes insipidus. We also review the relevant literature.