Transient D-Penicillamine-Induced Nephrogenic Diabetes Insipidus during Treatment of a Patient with Cystinuria —D-Penicillamine-Induced Nephrogenic Diabetes Insipidus

Background: Diabetes insipidus (DI) is a rare disorder characterized by inappropriate polyuria and hypo-osmolar urine. It is caused by inadequate production of antidiuretic hormone, in response to hypothalamic osmoreceptor-stimulation, from the pituitary gland (central DI) or resistance to its action at terminal distal convoluted tubules and collecting ducts (nephrogenic DI). Most cases of nephrogenic DI are caused by drugs, especially chronic lithium use. The Case: A 46-year-old man manifested such a disorder 8 months following d-Penicillamine (d-P) therapy for cystinuria. The drug was discontinued and the patient was managed conservatively with high fluid intake, diet low in protein and salt as well as alkalization of urine with Urolyte U to a pH > 7.5. Six weeks later, such side effect disappeared. Our patient had developed such phenomenon: a) without significant liver or renal disease to account for cumulative toxicity, and b) with a conventional dosage range of d-P. Such isolated toxicity indicates inherited a predisposition to this side effect. Conclusion: DI is a potential side effect of d-P therapy that is nephrogenic in site, transient in prognosis and an isolated phenomenon likely to reflect genetic predisposition.

Etiological Spectrum with Diagnosis and Prognosis of Central Diabetes Insipidus needs Long Term Followup:A Single Centre Experience

Introduction:Central Diabetes insipidus(CDI)is a rare disorder caused by vasopressin deficiency characterized by the excretion of copious volumes of unconcentrated urine.Objective:To assess the etiological,clinical,biochemical and radiological spectrum of Central DI in our institute and long term follow up of these cases.Material and Methods:32 patients with Central DI admitted in Department of Endocrinology,Guwahati Medical College,Assam in the last 2.5 years were included.Detailed clinical assessment,biochemical evaluation and MRI(Magnetic Resonance imaging)brain were done in all the patients.Central DI without any identifiable cause was considered Idiopathic and those with structural lesion in hypothalamic pituitary region were considered organic.Result:Idiopathic CDI was present in 12(37.5%)patients and 20(62.5%)patients had organic CDI with acute onset of presentation.12(60%)patients with organic CDI present with neurological symptoms but 8(40%)patients had no neurological symptoms even with organic cause.Pituitary dysfunction was common in organic CDI as compared to idiopathic CDI.Paediatric patients commonly present with organic cause for CDI with low cortisol most common hormonal deficit.One patient of idiopathic CDI with normal stalk thickness at baseline presented with clinical and radiological features of LCH(Langerhans cell histiocytosis)on follow up.Conclusion:Organic CDI more likely to have acute onset of presentation than idiopathic CDI and even in absence of neurological features.Paediatric patients commonly have organic cause for CDI.We propose the paramount importance of long-term clinical follow-up and reassessment of endocrine function in patients with CDI for definitive diagnosis of autoimmune and inflammatory causes of idiopathic CDI and timely treatment of pituitary hypofunction.

Mutation Analysis of AVPR2 and AQP2 Gene in Chinese Patients with Congenital Nephrogenic Diabetes Insipidus

To detect mutations of the aquaporin 2 gene（AQP2） and the arginine vasopressin V2 receptor gene（AVPR2） of Chinese congenital nephrogenic diabetes insipidus, and to establish the foundation for further studying the emergence mechanism of the disease and clinical diagnosis, all the exons and part of introns of AQP2 and AVPR2 genes were amplified with intronic primers, using genomic DNA extracted from three patients with congenital nephrogenic diabetes insipidus and two mothers as template, PCR product was ligated into a T-vector and then sequenced. The result was compared with the database sequence to identify the mutable sites via a BLAST search, the incidence of every mutation was analyzed, and the putative transcription factor binding sites that maybe disturbed were analyzed by MAPPER. Mutation g.1394A〉G in exon 3 of AVPR2 was detected in all the subjects, g.861C〉T（S167L） in exon 2 of AVPR2 and IVS1＋3G〉A in intron of AQP2 were detected, respectively, in two patients, and c.836A〉C in 3′ untranslated region of AQP2 was detected in two patients and one mother. Four mutations were identified. g.1394A〉G of AVPR2 and c.836A〉C of AQP2 have high incidence in patients with nephrogenic diabetes insipidus. Detection on the two sites may become auxiliary diagnosis index of congenital nephrogenic diabetes insipidus.

Diabetes insipidus with impaired vision caused by germinoma and perioptic meningeal seeding:A case report

BACKGROUND Germinoma is a type of germ cell tumor that most frequently arises in the midline axis of the brain.Impaired vision is a clinical manifestation of germinnoma.Although rare,intracranial germinoma seeding to the perioptic arachnoid space is one cause of visual acuity decrease.CASE SUMMARY An 11yearold girl who presented with polyuria and polydipsia and subsequently developed diminution of vision.Imaging showed bilateral heterogeneous enhancement of the optic nerve sheaths and atrophy of the optic nerve,and transsphenoidal biopsy revealed a germinoma.The patient experienced poor visual recovery following chemotherapy and radiotherapy.Germinomas are rare and they are mostly identified in children and adolescents.The manifestations include diabetes insipidus,pituitary dysfunction,visual complaints,etc.The mechanisms that lead to visual loss include intracranial hypertension,compression of optic chiasma,and tumor invasion.A literature review was performed to summarize the cases with a tumor infiltrating the optic nerve.Most of the reported patients were adolescents and presented with anterior pituitary hormone deficiency.Enhancement of optic nerve sheaths and optic disc pallor could be identified in most of the cases.The purpose of this report is to provide awareness that in cases where a germinoma is associated with visual loss,though rare,perioptic meningeal seeding should be taken into consideration.CONCLUSION The case report suggests that children with diabetes insipidus need a complete differential diagnosis.

Congenital nephrogenic diabetes insipidus due to the mutation in AVPR2(c.541C>T)in a neonate:A case report

BACKGROUND Congenital nephrogenic diabetes insipidus (CNDI) is a rare hereditary renaldisorder that is caused by mutations in AVPR2 or aquaporin 2 (AQP2). Up tonow, there are few reports about CNDI in neonates. Early clinical manifestationsof CNDI in neonates are atypical. A lack of understanding of the disease byclinicians causes frequent misdiagnoses or missed diagnoses, which may result infailure to administer treatments in time and ultimately leads to severecomplications. In this study, clinical data of a case of AVPR2 gene mutationinducedCNDI, which was confirmed by genetic testing, were retrospectivelyanalyzed to improve our understanding of this disease.CASE SUMMARY On February 1, 2020, a male neonate was hospitalized 17 d after birth due to a 7 dperiod of pyrexia. The patient’s symptoms included recurrent pyrexia,hypernatremia and hyperchloremia, which were difficult to treat. The patient wasfed on demand, and water was additionally provided between milk intakes. Acombination treatment of hydrochlorothiazide and amiloride was administered.After the treatment, body temperature and electrolyte levels returned to normal,the volume of urine was significantly reduced and the patient was subsequentlydischarged. Genetic tests confirmed that the patient carried the AVPR2 genemissense mutation c.541C>T (P.R181C), and the patient’s mother carried aheterozygous mutation at the same locus. After clinical treatment with acombination of hydrochlorothiazide and amiloride, the body temperature andelectrolyte levels returned to normal. Up until the most recent follow-up examination, normal body temperature, electrolyte levels and growth anddevelopment were observed.CONCLUSION CNDI in the neonatal period is rare, and its clinical manifestations are unspecificwith some patients merely showing recurrent fever and electrolyte disturbance.Genetic testing of AVPR2 and AQP2 can be used for screening and geneticdiagnosis of CNDI.

Congenital nephrogenic diabetes insipidus arginine vasopressin receptor 2 gene mutation at new site:A case report

BACKGROUND Congenital nephrogenic diabetes insipidus(CNDI)is a rare hereditary disorder.It is associated with mutations in the arginine vasopressin receptor 2(AVPR2)gene and aquaporin 2(AQP2)gene,and approximately 270 different mutation sites have been reported for AVPR2.Therefore,new mutations and new manifestations are crucial to complement the clinical deficiencies in the diagnosis of this disease.We report a case of a novel AVPR2 gene mutation locus and a new clinical manifestation.CASE SUMMARY We describe the case of a 48-d-old boy who presented with recurrent fever and diarrhea 5 d after birth.Laboratory tests showed electrolyte disturbances and low urine specific gravity,and imaging tests showed no abnormalities.Genetic testing revealed a novel X-linked recessive missense mutation,c.283(exon 2)C>T(p.P95S).This mutation results in the substitution of a proline residue with a serine residue in the AVPR2 protein sequence.The diagnosis of CNDI was confirmed based on the AVPR2 gene mutation.The treatment strategy for this patient was divided into two stages,including physical cooling supplemented with appropriate amounts of water in the early stage and oral hydrochlorothiazide(1-2 mg/kg)after a clear diagnosis.After follow-up of one and a half years,the patient gradually improved.CONCLUSION AVPR2 gene mutations in new loci and new clinical symptoms help clinicians understand this disease and shorten the diagnosis cycle.

Management of a Parturient with Preeclampsia and HELLP Syndrome Complicated by Gestational Diabetes Insipidus

HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) is considered to be a variant or severe form of pre-eclampsia, a life threatening complication of pregnancy. Gestational Diabetes Insipidus (GDI) can coexist with severe preeclampsia and HELLP syndrome. The combination of these two conditions presents a unique challenge to the anesthesiologist and the obstetric team, caring for this parturient. We present the case of a parturient with an unusual presentation of GDI, coexisting with severe preeclampsia and HELLP syndrome. She had two days history of polyuria and polydipsia as well as lethargy and rapidly rising serum sodium in addition to acute renal failure without any neurologic symptoms. Expeditious delivery of the baby and supportive management is essential for optimal outcomes. She underwent a repeat Cesarean section under combined spinal epidural (CSE) anesthesia. This patient was discharged on postoperative day five after clinical resolution of her signs and symptoms.

Mechanisms of hyponatremia and diabetes insipidus after acute spinal cord injury:a critical review

The incidence of hyponatremia after spinal cord injury was reported to be between 25 and 80%.Hyponatremia can lead to a variety of clinical symptoms,from mild to severe and even life-threatening.Hyponatremia is often associated with diabetes insipidus,which refers to insufficient arginine vasopressin(AVP)secretion or defective renal response to AVP,with clinical manifestations of syndromes such as hypoosmolality,polydipsia,and polydipsia.Recent mechanistic studies on hyponatremia and diabetes insipidus after acute spinal cord injury have been performed in isolation,without integrating the above two symptoms into different pathological manifestations that occur in the same injury state and without considering the acute spinal cord injury patient’s condition as a whole.The therapeutic principles of CSWS and SIADH are in opposition to one another.It is not easy to identify the mechanism of hyponatremia in clinical practice,which makes selecting the treatment difficult.According to the existing theories,treatments for hyponatremia and diabetes insipidus together are contraindicated,whether the mechanism of hyponatremia is thought to be CSWS or SIADH.In this paper,we review the mechanism of these two pathological manifestations and suggest that our current understanding of the mechanisms of hyponatremia and diabetes insipidus after high acute cervical SCI is insufficient,and it is likely that there are other undetected pathogenetic mechanisms.

Caution on diagnosis of idiopathetic central diabetes insipidus

Idiopathetic central diabetes insipidus （CDI） is a heterogeneous hypothalamus-pituitary disease due to the absence or deficiency of arginine vasopressin （AVP）.

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.

Multisystemic recurrent Langerhans cell histiocytosis misdiagnosed with chronic inflammation at the first diagnosis:A case report

BACKGROUND Langerhans cell histiocytosis(LCH)is characterized by diabetes insipidus and is an uncommon occurrence.Pathological biopsies still have a certain degree of diagnostic probability.We present a case in which LCH initially affected the pituitary gland.This resulted in a misdiagnosis of chronic inflammation upon pathological examination.CASE SUMMARY A 25-year-old female exhibited symptoms of diabetes insipidus.Magnetic resonance imaging revealed an enhanced foci in the pituitary gland.After surgical resection of the pituitary lesion,the pathological diagnosis was chronic inflam-mation.However,the patient later experienced bone destruction in the skull and lower limb bones.After the lower limb bone lesion was compared with the initial pituitary lesion,the final diagnosis was modified to LCH.The patient was treated with multiple chemotherapy courses.However,the patient’s condition gradually worsened,and she eventually passed away at home.CONCLUSION LCH should be considered when patients exhibit diabetes insipidus and absence of high signal intensity in the pituitary gland on sagittal T1-weighted image and abnormal enhancement in the pituitary region.

Prolonged hypernatremia triggered by hyperglycemic hyperosmolar state with coma: A case report

A man with past lithium use for more than 15 years, but off lithium for two years and not carrying the diagnosis of diabetes mellitus or nephrogenic diabetes insipidus(NDI), presented with coma and hyperglycemic hyperosmolar state(HHS). Following correction of HHS, he developed persistent hypernatremia accompanied by large volumes of urine with low osmolality and no response to desmopressin injections. Urine osmolality remained < 300 m Osm/kg after injection of vasopressin. Improvement in serum sodium concentration followed the intake of large volumes of water plus administration of amiloride and hydrochlorothiazide. Severe hyperglycemia may trigger symptomatic lithium-induced NDI years after cessation of lithium therapy. Patients with newonset diabetes mellitus who had been on prolonged lithium therapy in the past require monitoring of their serum sodium concentration after hyperglycemic episodes regardless of whether they do or do not carry the diagnosis of NDI.

Pulmonary Langerhans cell histiocytosis and multiple system involvement:A case report

BACKGROUND Pulmonary Langerhans cell histiocytosis(PLCH)is a relatively rare type of lung disease,common in middle-aged smoking men.It is characterized by proliferation and infiltration of Langerhans cells,and the formation of multiple parabronchial mesenchymal nodules in lung tissue,and may lead to organ dysfunction.There are no typical symptoms and signs,and it is easily misdiagnosed or missed,and therefore deserves clinical attention and further discussion.CASE SUMMARY We describe the case of a nonsmoking 46-year-old man with PLCH diagnosed based on clinical manifestations of fever and dry cough,with a history of hypothyroidism and diabetes insipidus for 9 years.Computed tomography(CT)-and CT-guided puncture examinations revealed no abnormalities,and he ultimately underwent thoracoscopic biopsy to confirm the diagnosis.The pathological diagnosis was PLCH.Thyroid function was maintained by medication.Pituitary magnetic resonance imaging showed that the pituitary stalk had become thinner.CONCLUSION LCH often involves multiple systems.Moreover,the pathogenesis is not clear,clinical manifestations lack specificity,and diagnosis requires special attention.Diagnosis of PLCH can significantly benefit from comprehensive multidisciplinary analysis.

Dexmedetomidine-induced polyuria in the intensive care unit: a case report

Dexmedetomidine is anα2 agonist that is frequently used for sedation in intensive care units(ICUs).Hypotension and bradycardia are common adverse effects observed in clinical practice.In perioperative conditions,polyuria is a rare adverse effect with limited case reports after dexmedetomidine infusion.Similar to this situation,in ICU,there are rare cases.We present the case of a 59-year-old man who developed polyuria secondary to high-dose intravenous dexmedetomidine infusion in the medical ICU.

Clinical features of patients with pituitary stalk thickening: a review of 159 cases from one medical center

Background:Pituitary stalk thickening (PST) used as an imaging diagnosis plays a major role in diagnosis and treatment of the hypothalamus and pituitary disease at an early stage.Up until now,several lines of systematic investigations have been conducted among adolescents,and the results indicated that PST is possibly one of the principal early manifestations of sellar region tumor.To characterize the major clinical features of PST and to identify the most effective treatments we conducted this study.Methods:This was a retrospective review of patients with PST evaluated at Huashan Hospital over an eight-year period between 2007 and 2014.One hundred fifty nine patients who were diagnosed PST were included.The data including demographics,clinical presentations,imaging examinations,laboratory results and surgery were thoroughly reviewed and carefully analyzed.According to their clinical presentations and examinations,relevant treatments were adopted and different prognosis were observed.Results:Of the 159 patients,57 were males and 102 were females (median age was 29 and 43.4％ were under the age of 21 years).And of the patients in the age group between 30 and 35 years,84％ were females.'Polydipsia and polyuria' was the most common clinical manifestation observed in 90 cases (＞50％).49.5％ of the patients were diagnosed to have at least one anterior pituitary dysfunction.The sellar region MRI (SR-MRI) data showed that patients who had different clinical presentations or pituitary function showed different SR-MRI appearance.Over 60％ patients who performed followup MRI showed shrunken PST.Fourteen cases who received radiotherapy appeared to be improved as shown by MRI.Conclusions:PST is most commonly seen in the teenagers and the women of reproductive age.Distinct etiology may be identified based on the clinical manifestations,age and SR-MRI,which would help to make the final decision for treatments.Radiotherapy and immuno-suppressed therapy are effective in alleviating clinical symptoms and shrinking the stalk thickening.

Changes of hypothalamus-pituitary hormones in patients after totalr emoval of craniopharyngiomas

Background This paper aimed to elucidate the changes of hypothalamus-pituitary hormones in patients after total removal of craniopharyngiomas. Methods A total of 40 patients with craniopharyngioma s received surgery. The levels of triiodothyronine (T3), thyroxine (T4), thyrotropic hormone (TSH), antidiuretic hormone (ADH), and adrenocorticotropin (ACTH) were measureed in the 40 patients b efore surgery and one week after surgery respectively. Results Twenty-eight patients (70%) had hypothyroidism before surgery, but 38 (95%) had hypothyroidism after surgery (P<0.01). Twenty-three patients (57.5%) had diabetes insipidus (DI) before surgery and 38(95%) had DI after surgery (P<0.001). The pre- and post-operative levels of ADH were (2.49±0.30) pg/ml and (2.80±0.29) pg/ml respectively (P>0.05), whereas tho se of ACTH were (23.97±2.69) pg/ml and (15.60±1.91) pg/ml respectively (P<0.05). Conclusions Hormone deficits after total removal of craniopharyngioma appear to be the common complication of surgery. Hypothyroidism and diabetes insipidus are more frequen t after surgery than before surgery. Thyroxine and glucocorticoids should be administered routinely after total removal of craniopharyngioma.