Multiple pituitary hormone deficiencies in a kitten: Hyposomatotropism, hypothyroidism, central diabetes insipidus and hypogonadism.

In humans, post-traumatic hypopituitarism (PTHP) is a common complication of traumatic brain injury, with the most frequently reported hormonal deficiencies resulting in hyposomatotropism and hypogonadism, followed by hypothyroidism, hypocortisolism, and central diabetes insipidus. To date, PTHP has rarely been reported in cats, and the reported cases often describe a single hormone deficiency. This report details an approximately 7-month-old cat with a history of suspected traumatic brain injury at 5 wk of age, that presented with growth retardation (1.53 kg) and polyuria-polydipsia. Thyroid panel, thyrotropin-releasing hormone stimulation test, thyroid scan with Technetium-99, repeat measurement of serum IGF-1, resting cortisol, endogenous ACTH concentration, and ACTH stimulation testing were performed. The cat was diagnosed with presumptive PTHP leading to hyposomatotropism, hypothyroidism, central diabetes insipidus, and hypogonadism. In this case, treatment of the hypothyroidism and central diabetes insipidus were successful. Hyposomatotropism and hypogonadism were not treated. Although reported feline PTHP cases have described a single hormone deficiency, this report details a cat with presumptive PTHP leading to hyposomatotropism, hypothyroidism, central diabetes insipidus, and hypogonadism. Attention should be paid to the potential for the development of PTHP in cats secondary to traumatic brain injury. Key clinical message: Post-traumatic hypopituitarism in cats can lead to multiple hormone deficiencies, leading to hyposomatotropism, hypothyroidism, central diabetes insipidus, and hypogonadism.

Insuffisances hormonales hypophysaires multiples chez un chaton : hyposomatotropisme, hypothyroïdie, diabète insipide central et hypogonadisme. En médecine humaine, l'hypopituitarisme post-traumatisme crânien (HPPT) est une complication fréquente après un trauma crânien. Les insuffisances hormonales les plus fréquemment rapportées sont l'hyposomatotropisme et l'hypogonadisme, suivis de l'hypothyroïdie, de l'hypocortisolisme et du diabète insipide central. À ce jour, l'HPPT a rarement été décrit chez le chat, et les cas publiés décrivent bien souvent une déficience hormonale unique. Dans le cas présent, un chat âgé d'environ 7 mois, avec un antécédent de trauma crânien suspecté à l'âge de 5 semaines, a été présenté avec un retard de croissance (1,53 kg) et un syndrome polyurie-polydipsique. Les examens d'endocrinologie complémentaires incluaient le dosage des hormones thyroïdiennes, la stimulation de l'hypophyse par la thyrolibérine, une scintigraphie thyroïdienne (Technetium-99), le dosage de l'IGF-1, du cortisol basal, de la concentration d'ACTH endogène, et un test de stimulation à l'ACTH. Le chat a été diagnostiqué de manière présomptive avec un HPPT causant de multiples insuffisances hormonales hypophysaires : hyposomatotropisme, hypothyroïdie, diabète insipide central et hypogonadisme. Chez ce chat, le traitement de l'hypothyroïdie et du diabète insipide central a été réussi. L'hyposomatotropisme et l'hypogonadisme n'ont pas été traités. Alors que les rapports de cas publiés sur l'HPPT félin décrivent souvent une seule déficience hormonale, ce chat a été diagnostiqué avec de multiples insuffisances hormonales hypophysaires. Les cliniciens doivent rester attentifs au développement potentiel d'un hypopituitarisme après un trauma crânien.Message clinique clé :L'hypopituitarisme post-traumatique chez le chat peut entraîner de multiples déficiences hormonales, entraînant un hyposomatotropisme, une hypothyroïdie, un diabète insipide central et un hypogonadisme.(Traduit par les auteurs).

Changing the Name of Diabetes Insipidus: A Position Statement of the Working Group for Renaming Diabetes Insipidus.

Recent data show that patients with a diagnosis of diabetes insipidus (DI) are coming to harm. Here we give the rationale for a name change to arginine vasopressin deficiency and resistance for central and nephrogenic DI, respectively.

Management of cranial diabetes insipidus: clinical outcomes and patient perception of care.

Objective: There is growing recognition of morbidity and mortality that can occur in patients with cranial diabetes insipidus (CDI) during hospitalisation, due to prescribing errors and dysnatraemia, often related to confusion between CDI and diabetes mellitus among non-specialists. We aimed to investigate this. Methods: Data for each hospitalisation in patients with CDI attending Oxford University Hospital (OUH) were collected retrospectively. The same cohort were invited to complete a questionnaire by telephone. Results: One hundred and nine patients were included, median age was 42 (range: 6-80) years. Route of desmopressin was tablet, melt and nasal spray in 74%, 7% and 17% of patients, respectively, while two patients used a combination of tablet and nasal spray. There were 85 admissions to OUH by 38 patients between 2012 and 2021. Daily measurement of serum sodium was performed in 39% of admissions; hyponatraemia and hypernatraemia occurred in 44 and 15% of admissions, respectively. Endocrine consultation was sought in 63% of admissions post-2018. Forty-five of 78 patients (58%) self-reported ≥1 admission to any hospital since diagnosis. Of these, 53% felt their medical team did not have a good understanding of the management of CDI during hospital admission. Twenty-four per cent reported delay in administration of desmopressin, while 44% reported confusion between CDI and diabetes mellitus, often leading to unnecessary blood glucose monitoring. Conclusion: Dysnatraemia is common in hospitalised patients with CDI. More than half of patients perceived their medical team's understanding of CDI to be poor when admitted with intercurrent illness. A coordinated approach, including early consultation of specialists, frequent serum sodium monitoring, and education of hospital specialists is needed to address this.

Diagnosis and Management of Central Diabetes Insipidus in Adults.

Central diabetes insipidus (CDI) is a clinical syndrome which results from loss or impaired function of vasopressinergic neurons in the hypothalamus/posterior pituitary, resulting in impaired synthesis and/or secretion of arginine vasopressin (AVP). AVP deficiency leads to the inability to concentrate urine and excessive renal water losses, resulting in a clinical syndrome of hypotonic polyuria with compensatory thirst. CDI is caused by diverse etiologies, although it typically develops due to neoplastic, traumatic, or autoimmune destruction of AVP-synthesizing/secreting neurons. This review focuses on the diagnosis and management of CDI, providing insights into the physiological disturbances underpinning the syndrome. Recent developments in diagnostic techniques, particularly the development of the copeptin assay, have improved accuracy and acceptability of the diagnostic approach to the hypotonic polyuria syndrome. We discuss the management of CDI with particular emphasis on management of fluid intake and pharmacological replacement of AVP. Specific clinical syndromes such as adipsic diabetes insipidus and diabetes insipidus in pregnancy as well as management of the perioperative patient with diabetes insipidus are also discussed.

[Central diabetes insipidus]. / Diabète insipide central.

"Central diabetes insipidus Diabetes insipidus may remain undetected for a long time, the ionogram remaining normal as long as polydipsia compensates for diuresis. In the first place, and by argument of frequency, polyuria should rule out diabetes. Diabetes insipidus is evoked in the presence of an incapacitating polyuro polydipsic syndrome, especially at night. Pituitary MRI eliminate a tumoral or infiltrative cause and confirm a central cause by the disappearance of the physiological t1 hypersignal in the post-pituitary gland. A water restriction test should only be performed in a hospital setting under close supervision. Lifetime hormone replacement therapy is appropriate in situations of pregnancy, risk of dehydration, and signs of overdose must be known by the patient, who must be educated about his or her disease."

"Diabète insipide central Le diabète insipide peut rester longtemps inaperçu, l'ionogramme restant normal tant que la polydipsie compense la diurèse. En premier lieu, et par argument de fréquence, une polyurie doit faire éliminer un diabète. Le diabète insipide est évoqué devant un syndrome polyuro-polydipsique invalidant, notamment nocturne. L'IRM hypophysaire a alors deux objectifs : éliminer une cause tumorale ou infiltrative et affirmer une cause centrale par la disparition de l'hypersignal t1 physiologique au niveau de la post-hypophyse. Un test de restriction hydrique ne doit être réalisé qu'en milieu hospitalier sous surveillance rapprochée. Le traitement hormonal substitutif à vie est adapté dans les situations de grossesse, de risque de déshydratation et les signes de surdosage doivent être connus du patient, éduqué à sa maladie."

Approach to the Pediatric Patient: Central Diabetes Insipidus.

Central diabetes insipidus (CDI) is a complex disorder in which large volumes of dilute urine are excreted due to arginine-vasopressin deficiency, and it is caused by a variety of disorders affecting the hypothalamic-posterior pituitary network. The differential diagnosis is challenging and requires a detailed medical history, physical examination, biochemical approach, imaging studies, and, in some cases, histological confirmation. Magnetic resonance imaging is the gold standard method for evaluating congenital or acquired cerebral and pituitary stalk lesions. Pituitary stalk size at presentation could be normal, but it may change over time, depending on the underlying condition, while other brain areas or organs may become involved during follow-up. Early diagnosis and treatment are crucial to avoid central nervous system damage and germ cell tumor dissemination and to minimize complications of multiple pituitary hormone defects. We provide a practical update on the diagnosis and management of patients with CDI and highlight several pitfalls that may complicate the differential diagnosis of conditions presenting with polyuria and polydipsia. The need for a careful and close follow-up of patients with apparently idiopathic CDI is particularly emphasized because the underlying condition may be recognized over time. The clinical scenario that we outline at the beginning of this article represents the basis for the discussion about how the etiological diagnosis of CDI can be overlooked and demonstrates how a water intake and urine output improvement can be a sign of progressive damage of both hypothalamus and anterior pituitary gland with associated pituitary hormonal deficiencies.

Adipsic Diabetes Insipidus in Children: A Case Report and Practical Guide.

BACKGROUND Diabetes insipidus (DI) is a clinical syndrome characterized by polyuria and polydipsia that result from a deficiency of antidiuretic hormone (ADH), central DI, or resistance to ADH, nephrogenic DI. In otherwise healthy patients with DI, normal thirst mechanism, and free access to water, the thirst system can maintain plasma osmolality in the near-normal range. However, in cases where DI presents with adipsia, cognitive impairment, or restricted access to water, true hypernatremia may occur, leading to severe morbidity and mortality. CASE REPORT We report a case of a 2-year-old boy who had global developmental delay and post-brain debulking surgery involving the hypothalamic region, which resulted in central DI and thirst center dysfunction. We describe the clinical presentation, the current understanding of adipsic DI, and a new practical approach for management. The main guidelines of treatment include (1) fixed desmopressin dosing that allows minimal urinary breakthroughs in-between the doses; (2) timely diaper weight-based replacement of water; (3) bodyweight-based fluid correction 2 times a day, and (4) providing the nutritional and water requirements in a way similar to any healthy child but at fixed time intervals. CONCLUSIONS This plan of management showed good effectiveness in controlling plasma sodium level and volume status of a child with adipsic DI without interfering with his average growth. This home treatment method is practical and readily available, provided that the family remains very adherent.

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.

Acquired forms of central diabetes insipidus: Mechanisms of disease.

Most cases of acquired central diabetes insipidus are caused by destruction of the neurohypophysis by: 1) anatomic lesions that destroy the vasopressin neurons by pressure or infiltration, 2) damage to the vasopressin neurons by surgery or head trauma, and 3) autoimmune destruction of the vasopressin neurons. Because the vasopressin neurons are located in the hypothalamus, lesions confined to the sella turcica generally do not cause diabetes insipidus because the posterior pituitary is simply the site of the axon terminals that secrete vasopressin into the bloodstream. In addition, the capacity of the neurohypophysis to synthesize vasopressin is greatly in excess of the body's needs, and destruction of 80-90% of the hypothalamic vasopressin neurons is required to produce diabetes insipidus. As a result, even large lesions in the sellar and suprasellar area generally are not associated with impaired water homeostasis until they are surgically resected. Regardless of the etiology of central diabetes insipidus, deficient or absent vasopressin secretion causes impaired urine concentration with resultant polyuria. In most cases, secondary polydipsia is able to maintain water homeostasis at the expense of frequent thirst and drinking. However, destruction of the osmoreceptors in the anterior hypothalamus that regulate vasopressin neuronal activity causes a loss of thirst as well as vasopressin section, leading to severe chronic dehydration and hyperosmolality. Vasopressin deficiency also leads to down-regulation of the synthesis of aquaporin-2 water channels in the kidney collecting duct principal cells, causing a secondary nephrogenic diabetes insipidus. As a result, several days of vasopressin administration are required to achieve maximal urine concentration in patients with CDI. Consequently, the presentation of patients with central diabetes insipidus can vary greatly, depending on the size and location of the lesion, the magnitude of trauma to the neurohypophysis, the degree of destruction of the vasopressin neurons, and the presence of other hormonal deficits from damage to the anterior pituitary.

Central diabetes insipidus in children: Diagnosis and management.

Central diabetes insipidus (CDI) is a complex disorder in which large volumes of dilute urine are excreted due to arginine-vasopressin deficiency, and it is caused by a variety of conditions (genetic, congenital, inflammatory, neoplastic, traumatic) that arise mainly from the hypothalamus. The differential diagnosis between diseases presenting with polyuria and polydipsia is challenging and requires a detailed medical history, physical examination, biochemical approach, imaging studies and, in some cases, histological confirmation. Magnetic resonance imaging is the gold standard method for evaluating the sellar-suprasellar region in CDI. Pituitary stalk size at presentation is variable and can change over time, depending on the underlying condition, and other brain areas or other organs - in specific diseases - may become involved during follow up. An early diagnosis and treatment are preferable in order to avoid central nervous system damage and the risk of dissemination of germ cell tumor, or progression of Langerhans Cell Histiocytosis, and in order to start treatment of additional pituitary defects without further delay. This review focuses on current diagnostic work-up and on the role of neuroimaging in the differential diagnosis of CDI in children and adolescents. It provides an update on the best approach for diagnosis - including novel biochemical markers such as copeptin - treatment and follow up of children and adolescents with CDI; it also describes the best approach to challenging situations such as post-surgical patients, adipsic patients, patients undergoing chemotherapy and/or in critical care.

ENDOCRINOLOGY IN THE TIME OF COVID-19: Management of diabetes insipidus and hyponatraemia.

COVID-19 has changed the nature of medical consultations, emphasizing virtual patient counseling, with relevance for patients with diabetes insipidus (DI) or hyponatraemia. The main complication of desmopressin treatment in DI is dilutional hyponatraemia. Since plasma sodium monitoring is not always possible in times of COVID-19, we recommend to delay the desmopressin dose once a week until aquaresis occurs allowing excess retained water to be excreted. Patients should measure their body weight daily. Patients with DI admitted to the hospital with COVID-19 have a high risk for mortality due to volume depletion. Specialists must supervise fluid replacement and dosing of desmopressin. Patients after pituitary surgery should drink to thirst and measure their body weight daily to early recognize the development of the postoperative syndrome of inappropriate antidiuresis (SIAD). They should know hyponatraemia symptoms. The prevalence of hyponatraemia in patients with pneumonia due to COVID-19 is not yet known, but seems to be low. In contrast, hypernatraemia may develop in COVID-19 patients in ICU, from different multifactorial reasons, for example, due to insensible water losses from pyrexia, increased respiration rate and use of diuretics. Hypernatraemic dehydration may contribute to the high risk of acute kidney injury in COVID-19. IV fluid replacement should be administered with caution in severe cases of COVID-19 because of the risk of pulmonary oedema.

Gestational diabetes insipidus: Diagnosis and management.

In the pregnant patient, hypotonic polyuria in the setting of elevated serum osmolality and polydipsia should narrow the differential to causes related to diabetes insipidus (DI). Gestational DI, also called transient DI of pregnancy, is a distinct entity, unique from central DI or nephrogenic DI which may both become exacerbated during pregnancy. These three different processes relate to vasopressin, where increased metabolism, decreased production or altered renal sensitivity to this neuropeptide should be considered. Gestational DI involves progressively rising levels of placental vasopressinase throughout pregnancy, resulting in decreased endogenous vasopressin and resulting hypotonic polyuria worsening through the pregnancy. Gestational DI should be distinguished from central and nephrogenic DI that may be seen during pregnancy through use of clinical history, urine and serum osmolality measurements, response to desmopressin and potentially, the newer, emerging copeptin measurement. This review focuses on a brief overview of osmoregulatory and vasopressin physiology in pregnancy and how this relates to the clinical presentation, pathophysiology, diagnosis and management of gestational DI, with comparisons to the other forms of DI during pregnancy. Differentiating the subtypes of DI during pregnancy is critical in order to provide optimal management of DI in pregnancy and avoid dehydration and hypernatremia in this vulnerable population.

Management of central diabetes insipidus.

The treatment of central diabetes insipidus has not changed significantly in recent decades, and dDAVP and replacement of free water deficit remain the cornerstones of treatment. Oral dDAVP has replaced nasal dDAVP as a more reliable mode of treatment for chronic central diabetes insipidus. Hyponatraemia is a common side effect, occurring in one in four patients, and should be avoided by allowing a regular break from dDAVP to allow a resultant aquaresis. Hypernatraemia is less common, and typically occurs during hospitalization, when access to water is restricted, and in cases of adipsic DI. Management of adipsic DI can be challenging, and requires initial inpatient assessment to establish dose of dDAVP, daily fluid prescription, and eunatraemic weight which can guide day-to-day fluid targets in the long-term.

Acute myeloid leukemia with central diabetes insipidus.

While acute myeloid leukemia (AML) is the most common type of acute leukemia in adulthood, the constellation of AML associated with central diabetes insipidus (CDI) is rare and typically occurs in patients with chromosome 3 or 7 abnormalities. This subgroup of AML is associated with a poor clinical outcome. In this report, we present a young woman with AML and concurrent CDI in the presence of inversion(3)(q21q26). The AML was refractory to the induction therapy "7 + 3". Afterwards, the patient underwent allogenic stem cell transplantation (alloHSCT) and is still remaining in complete remission (CR) from AML as well as CDI 440 days after alloHSCT. Subsequently, in the largest study concerning patients with AML and CDI reported so far, we discuss additional cases from the literature. We demonstrated that patients with AML and CDI belong to the adverse prognostic group and clearly benefit from alloHSCT.

Diagnosis and management of central diabetes insipidus in adults.

Central diabetes insipidus (CDI) is characterized by hypotonic polyuria due to impairment of AVP secretion from the posterior pituitary. In clinical practice, it needs to be distinguished from renal resistance to the antidiuretic effects of AVP (nephrogenic DI), and abnormalities of thirst appreciation (primary polydipsia). As nephrogenic diabetes insipidus is rare in adults, unless they are treated with lithium salts, the practical challenge is how to differentiate between CDI and clinical disorders of excess thirst. The differential diagnosis is usually straight forward, but the recommended gold standard test, the water deprivation test, is not without interpretative pitfalls. The addition of the measurement of plasma AVP concentrations improves diagnostic accuracy, but the radioimmunoassay for AVP is technically difficult, and is only available in a few specialized centres. More recently, the measurement of plasma copeptin concentrations has been claimed to provide a reliable alternative to measurement of plasma AVP, without the sampling handling challenges. In addition, the measurement of thirst ratings can help the differentiation between CDI and primary polydipsia. Once the diagnosis of CDI is biochemically certain, investigations to determine the cause of AVP deficiency are needed. In this review, we will outline the diagnostic approach to polyuria, revisit the caveats of the water deprivation test and review recent data on value of adding AVP/copeptin measurement. We will also discuss treatment strategies for CDI, with analysis of potential complications of treatment.

Relation between change in treatment for central diabetes insipidus and body weight loss.

BACKGROUND: Patients with central diabetes insipidus (CDI) are known to lose weight because their polydipsia interferes with their nutritional intake. We retrospectively examined weight changes in CDI patients when they switched from nasal to oral desmopressin. METHODS: Twenty-three patients with CDI were included. Weight change was defined as an increase or decrease of more than 3 kg or 3% body weight. As factors contributing to the weight change, we studied the patients' clinical characteristics and quality of life (QOL) scores as determined by our original questionnaire. RESULTS: Five patients showed a weight loss of 5.9 kg (2.4-9.0 kg), and two patients showed weight gain, while 16 out of 23 patients were weight neutral. When the patients with weight gain and weight neutral were analyzed together, the mean weight change was +0.3 kg (-0.5 to +1.1 kg). All the patients who lost weight had a Body Mass Index ≥22 kg/m2 (38% vs. 0%, P=0.027) and higher frequencies of abnormally high serum levels of AST (40% vs. 0%, P=0.005). The sum of the QOL scores was similar between the two groups, but higher in patients who lost weight after switching to oral desmopressin (43.3±2.7) than in those who did not (38.2±5.0, P=0.01). CONCLUSIONS: Switching the treatment from nasal to oral desmopressin may cause weight loss in patients with CDI who seemed to have polydipsia-associated weight gain.

Cerebral tuberculomas in a 6-year-old girl causing central diabetes insipidus.

A 6-year-old girl presented acutely with worsening frontal headaches. She had a 3-month history of lethargy, reduced appetite, weight loss, cough and intermittent fevers. A chest X-ray showed a left upper lobe consolidation, and a CT head showed multiple enhancing lesions with significant surrounding oedema in both cerebral hemispheres. Due to the strong suspicion of tuberculosis (TB), she was admitted and treated with anti-TB therapy and steroids. Following this, pulmonary infection with Mycobacterium tuberculosis was confirmed by a positive PCR from induced sputum. Cerebral spinal fluid (CSF) analysis was normal and tested negative for M. tuberculosis on PCR. During her first week of treatment, she developed polyuria, nocturia and polydipsia and was diagnosed with central diabetes insipidus. She was started on desmopressin which rapidly improved her symptoms, and she was continued on desmopressin for 3 months. Currently, she remains well and has shown a good response to TB treatment.

Double Trouble - Severe Hypernatremia Secondary to Central Diabetes Insipidus Complicated by Hypercalcemic Nephrogenic Diabetes Insipidus: A Case Report.

BACKGROUND Patients with malignancies often have electrolyte abnormalities. We present a case of a patient with central diabetes insipidus secondary to metastatic pituitary invasion complicated by hypercalcemic nephrogenic diabetes insipidus. CASE REPORT We present a case of 40-year-old female with a history of stage IV breast cancer with skeletal and leptomeningeal metastasis, who was admitted with polyuria, polydipsia, and recent onset of confusion. The patient was found to have profound hypernatremia and severe hypercalcemia with normal parathyroid and vitamin D serum levels. Urine studies showed low urine osmolality and high urine output, despite the higher serum osmolality. The patient received 5% dextrose for rehydration, 1 dose of intravenous (IV) pamidronate, 1 dose of IV desmopressin, and 4 days of subcutaneous calcitonin 200 international units Q12H. Initially, her urine output in the hospital was in the range of 350-400 milliliters/hour, which responded well to 1 dose of 1-desamino-8d-arginine vasopressin (DDAVP). In the subsequent days, her confusion resolved with normalization of serum sodium and calcium, but she died because of the extensive malignancy. CONCLUSIONS Our case emphasizes the importance of identification of causes and complications of electrolyte abnormalities associated with metastatic cancers. These electrolyte abnormalities can be primary or paraneoplastic and should be actively pursued and treated in such cases.