Central Diabetes Insipidus: A Case Series and Literature Review

Vikram Singh Shekhawat; Amit Kumar Das; Somnath Pan; MD Sudhan

doi:10.4103/jmms.jmms_124_21

CASE SERIES

Year : 2022 | Volume : 24 | Issue : 2 | Page : 190-194

Central Diabetes Insipidus: A Case Series and Literature Review

Vikram Singh Shekhawat¹, Amit Kumar Das², Somnath Pan³, MD Sudhan⁴
¹ Department of Endocrinology, INHS ASVINI, Mumbai, Maharashtra, India
² Department of Pathology, INHS ASVINI, Mumbai, Maharashtra, India
³ Department of Radiology, INHS ASVINI, Mumbai, Maharashtra, India
⁴ Department of Neurosurgery, INHS ASVINI, Mumbai, Maharashtra, India

Date of Submission	28-Sep-2021
Date of Decision	04-Nov-2021
Date of Acceptance	17-Nov-2021
Date of Web Publication	01-Apr-2022

Correspondence Address:
(Dr) Vikram Singh Shekhawat
Department of Endocrinology, INHS Asvini, Mumbai, Maharashtra
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jmms.jmms_124_21

Abstract

Central diabetes insipidus (CDI) is a rare disorder of water homeostasis characterized by the excretion of a large volume of hypotonic urine resulting from deficient secretion of arginine vasopressin. It is the most common form of diabetes insipidus and manifests when more than 90% of the vasopresinergic magnocellular neurons have been destroyed. The correct diagnosis is always a challenge as it is not always possible to differentiate the different etiologies of CDI based on clinical, hormonal, and radiological examination alone. Histopathology may have to be resorted to at times to provide a definitive diagnosis. In this case series we describe five patients of CDI with varied aetioogies who presented to our tertiary centre. The case series describes and discusses the clinical presentation, evaluation and management of these patients who presented with diabetes insipidus. The aetiologies discussed are extremely rare and required histopathological examination for the final confirmation of diagnosis.

Keywords: Arginine vasopressin, central diabetes insipidus, craniopharyngioma, lymphocytic hypophysitis, polyuria, tubercular hypophysitis

How to cite this article:
Shekhawat VS, Das AK, Pan S, Sudhan M D. Central Diabetes Insipidus: A Case Series and Literature Review. J Mar Med Soc 2022;24:190-4

How to cite this URL:
Shekhawat VS, Das AK, Pan S, Sudhan M D. Central Diabetes Insipidus: A Case Series and Literature Review. J Mar Med Soc [serial online] 2022 [cited 2023 Mar 21];24:190-4. Available from: https://www.marinemedicalsociety.in/text.asp?2022/24/2/190/342372

Introduction

Central diabetes insipidus (CDI) is a disorder characterized by the excretion of a large volume of hypotonic urine due to the deficiency of the hormone arginine vasopressin (AVP).^[1] Acquired causes of CDI are more common than hereditary causes and usually include trauma, tumor, infections, inflammatory, and vascular disorders afflicting the hypothalamic-pituitary region. Evaluation involves taking a thorough history, clinical examination, confirming polyuria (urine output >50 ml/kg), and differentiating it from other subtypes of diabetes insipidus based on serum sodium, urine and serum osmolality, and water deprivation test. Differentiating one etiology of CDI from the others may not always be possible even after neuroimaging and histopathology may give the final answer in such cases. The treatment decision is complex and is largely dependent on ascertaining the correct etiology. The spectrum of causes is vast with overlapping clinical, hormonal, and radiological features and hence leads to a diagnostic dilemma. In this case series, we describe a spectrum of cases of CDI with varied etiologies, including some rare causes.

Case Reports

Case 1

An 18-year-old boy presented with history of intermittent throbbing headache for the past 5 years and polyuria and polydipsia of 10 months duration. Clinically, he had features of hypogonadism with testicular volume of 2 ml bilateral. Magnetic resonance imaging (MRI) revealed sellar-suprasellar cystic mass lesion [Figure 1]a. Hormonal evaluation revealed panhypopituitarism and CDI [Table 1]. He was treated with hydrocortisone, levothyroxine, and desmopressin therapy. He underwent transsphenoidal surgery to remove the sellar mass. Histopathological examination was consistent with craniopharyngioma, adamantinomatous type [Figure 1]b. Postsurgery, he was also started on injection human menopausal gonadotropins.

Table 1: Investigation profile of all cases in preoperative state (serum electrolytes and urine and serum osmolality of case 5 are in postoperative state)

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Figure 1: (a) Magnetic resonance imaging T1-weighted image (coronal view) with contrast showing suprasellar cystic mass lesion with rim enhancement. (b) Photomicrograph showing giant cells and hemosiderin-laden macrophages (H and E 400X) consistent with adamantinomatous craniopharyngioma

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Case 2

A 38-year-old male presented with complaints of episodic headache of 3 months duration, and polyuria and polydipsia of 1-month duration. Clinical examination was unremarkable. Hormonal evaluation revealed multiple anterior pituitary hormone deficiencies and CDI [Table 1]. MRI revealed intense homogeneously enhancing sellar mass with thickened infundibular stalk [Figure 2]a. A presumptive diagnosis of lymphocytic hypophysitis (LH) was made based on his clinical, biochemical, and radiological features. He was started on oral prednisolone (60 mg daily). However, he continued to have progressively worsening headache associated with vomiting. Repeat MRI at 4 weeks showed further increase in the size of the sellar mass. Consequently, 4 weeks after starting prednisolone, he underwent transsphenoidal surgery to remove the sellar mass. Histomorphology and immunohistochemistry (IHC) were suggestive of LH [Figure 2]b. Postoperatively, he continues to require multiple anterior pituitary hormone replacement therapy and desmopressin.

Figure 2: (a) Magnetic resonance imaging T1-weighted image (coronal view) with contrast showing an intense homogeneously enhancing sellar mass with thickened infundibular stalk. (b) Photomicrograph showing diffuse infiltration of the pituitary gland by CD 3 and CD 20 positive reactive lymphocytes on immunohistochemistry

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Case 3

A 30-year-old female presented with history of headache. She sought medical advice and was advised to take oral analgesics, with which her headache used to improve. However, gradually over the next 2 months, her headache progressively worsened, and she developed acute-onset painless loss of vision in her left eye, polyuria, and polydipsia. Ophthalmological examination revealed temporal hemianopia in the left eye, following which she underwent MRI brain, which revealed a sellar mass with suprasellar extension compressing and displacing the optic chiasma [Figure 3]a. Subsequent evaluation revealed multiple anterior pituitary hormone deficiencies and CDI [Table 1]. She underwent surgery, and the sellar mass was removed. Histology of the resected tissue revealed a necrotizing granulomatous hypophysitis [Figure 3]b. No microorganisms were identified with Ziehl-Neelsen stain; however, TB polymerase chain reaction was positive. Investigations showed erythrocyte sedimentation rate 54 mm fall in 1^st h, Mantoux test 22 mm, serum angiotensin-converting enzyme levels 18 U/L (12–68 U/L), antineutrophil cytoplasmic antibody (c-ANCA/p-ANCA), and viral markers were negative. Contrast-enhanced computed tomography chest and abdomen depicted centrilobular nodular opacities in the anterior basal segment of left lower lobe lung and significant mediastinal and hepatogastric lymphadenopathy suggestive of tuberculosis (TB). She was diagnosed to have disseminated tuberculosis with tubercular hypophysitis. She was treated with anti-tubercular and hormone replacement therapy. After 12 months of therapy, her secondary hypothyroidism, hypocortisolism, and CDI persists, but her lung lesions and lymphadenopathy have resolved completely. Follow-up MRI showed no residual lesion in the sella.

Figure 3: (a) Magnetic resonance imaging T1-weighted image (sagittal view) with contrast showing a sellar lesion with central necrosis. (b) Photomicrograph shows necrotizing granulomas with epithelioid cells, multinucleated giant cells, and lymphocytes (H and E 400X) consistent with tubercular hypophysitis

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Case 4

A 22-year-old male presented with complaints of low-to moderate-grade intermittent fever of 1-month duration associated with severe headache, polyuria, and polydipsia of 15 days duration and altered sensorium of 1-day duration. His parents also reported excessive eating and behavioral changes for 3 months. Evaluation revealed pancytopenia, multiple anterior pituitary hormone deficiencies and CDI [Table 1]. Neuroimaging revealed hypothalamic mass lesion [Figure 4]a. Cerebrospinal fluid (CSF), alpha-fetoprotein and beta-human chorionic gonadotropin (β-HCG) were normal. He underwent transsphenoidal surgery to remove the mass. Histopathology and IHC (cells strongly immunoreactive for LCA, CD 20) of the lesion were suggestive of primary central nervous system (CNS) lymphoma [Figure 4]b. He received high-dose methotrexate-based chemotherapy but unfortunately developed intracerebral hemorrhage and succumbed to his illness.

Figure 4: (a) Magnetic resonance imaging T1-weighted image (coronal view) with contrast showing an intensely enhancing suprasellar hypothalamic mass. (b) High power shows lymphoid cells dispersed throughout with increased cellular pleomorphism and angiocentric pattern (H and E 400X)

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Case 5

A 45-year-old male presented with history of headache associated with decreased vision in the right eye of 3 months duration. MRI brain revealed a large sellar mass lesion with suprasellar extension compressing the optic chiasma [Figure 5]a. Evaluation revealed GH, gonadotropin, and thyrotropin deficiency. He underwent transsphenoidal surgery to remove the sellar mass. Histopathology and IHC were consistent with nonfunctioning pituitary adenoma [Figure 5]b. Evaluation 4 weeks after surgery also revealed CDI [Table 1]. He continues to require hormone replacement to treat GH, gonadotropin, and thyrotropin deficiency, besides oral desmopressin.

Figure 5: (a) Magnetic resonance imaging T1-weighted image (coronal view) with contrast showing a large sellar mass with suprasellar extension. (b) Photomicrograph showing sheets of tumor cells with few pseudopapillae (100X) confirming pituitary adenoma

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Discussion

DI is a clinical syndrome characterized by the excretion of a large volume of hypotonic urine due to the inability of the kidneys to concentrate urine.^[1] DI is rare in general population with an estimated prevalence of 1 in 25,000.^[2] It can affect an individual at any time during life and occurs in both sexes equally. The four main subtypes of DI are CDI, nephrogenic DI, dipsogenic DI, and gestational DI. CDI is the most common form of DI and results from deficient secretion of the hormone AVP. AVP is a nonapeptide secreted by the magnocellular neurons in the hypothalamus. Its principal physiologic effect is retention of water in the body.^[3] It stimulates the V2 receptors on the basolateral membrane of principal cells in the kidneys to increase the tubular fluid permeability by stimulating exocytic insertion of protein water channels (aquaporin 2). AVP deficiency results in the patient passing large volumes of dilute urine, predisposing them to the risk of developing electrolyte abnormalities and dehydration. The patient manifests with DI only when more than 90% of the vasopressin magnocellular neurons have been destroyed. Most of the patients in states of AVP deficiency can however maintain their water balance invariably at the expense of marked polyuria and polydipsia.

CDI is more commonly an acquired disorder resulting from damage to the AVP-producing magnocellular neurons. This may result from neoplasias (craniopharyngioma, germinoma, and metastases), infections (TB, meningitis, and encephalitis), autoimmune disorders (lymphocytic infundibuloneurohypophysitis), trauma, vascular pathology (hypothalamic hemorrhage, infarction, or ligation of anterior communicating artery), and hydrocephalus or midline cerebral malformations.^[1] Hereditary forms of CDI caused by mutation of the AVP gene are less common and account for <10% of cases. About 25% of cases of CDI are idiopathic. Various pathological conditions causing CDI provide the physicians with a challenging diagnostic conundrum. It is not always possible to differentiate one pathology from the other based on clinical manifestations, hormonal profiles, and radiological findings. Histopathology may be required to confirm the diagnosis. Important risk factors for CDI include granulomatous disease, lymphocytic infundibuloneurohypophysitis, metastatic pituitary tumors, surgical resection of large suprasellar tumors such as craniopharyngioma or Rathke's cleft cyst, and traumatic brain injury. Clinical manifestations of CDI most commonly include sudden-onset polyuria, nocturia, and a compensatory polydipsia. They may also present with headache, nausea, vomiting, visual disturbances, and cranial nerve palsies due to pressure effects of the enlarged pituitary. Clinical manifestations of the deficient anterior pituitary hormone and systemic disease resulting in CDI may also be present. Biochemical evidence of one or more anterior pituitary hormone deficiency can be seen in 50%–60% of patients, with growth hormone, thyrotropin, and gonadotropin deficiencies being more common than the others.^[4]

Evaluation of a suspected case of DI first requires confirmation of significant polyuria (urine output >50 ml/kg/d) and exclusion of osmotic diuresis, diuretic use, and urinary tract infection. Once hypotonic polyuria is confirmed, the next step involves distinguishing between various subtypes of DI, which is critical for making the optimal treatment decision. This can be done using serum sodium, serum and urine osmolality, and water deprivation test. AVP and copeptin have also emerged as promising biomarkers for distinguishing various subtypes of DI; however, they are limited by their universal availability and standardization. Evaluation of CDI is incomplete without MRI of the hypothalamic-pituitary region and evaluation of anterior pituitary hormones.^[1],[3] Desmopressin, a synthetic analog of AVP is the treatment of choice for patients with CDI. It is available in the form of nasal spray, oral tablets, and injections. The goal of therapy in treatment of CDI is to minimize polyuria/polydipsia to a degree that it does not interfere with the patient's normal lifestyle without predisposing him to an unwarranted risk of hyponatremia due to overtreatment.

Craniopharyngioma is a rare, benign, and slow-growing epithelial tumor. It is the most common neoplasms afflicting the hypothalamic–pituitary region in children and adolescents and accounts for 5%–15% of all the primary intracranial neoplasms in this age group. The most common age at presentation is 5–15 years and 50–74 years.^[5] Histologically, craniopharyngiomas can be divided into two main types, the more common adamantinomatous type, which is more common in young children, and the papillary type. The most common clinical manifestations are due to the mass effects of the lesion. Endocrine dysfunctions are present in 80%–90% of these patients at presentation.^[6] Growth hormone and gonadotropin deficiency are the most common deficiencies observed. CDI is present in 6%–38% of the patient at diagnosis, and approximately 90% develop CDI following surgery to remove craniopharyngioma.^[7] Neuroimaging is characterized by solid-cystic mass in sellar-suprasellar region. Calcification may be seen in half of these patients, especially children. Our patient had headache and CDI as the presenting manifestation, and evaluation revealed panhypopituitarism due to craniopharyngioma (adamantinomatous type).

LH is a rare inflammatory disorder of the pituitary. Based on the anatomic part of the pituitary gland involved, LH is classified into lymphocytic adenohypophysitis, lymphocytic infundibuloneurohypophysitis, and lymphocytic pan-hypophysitis (LPH). LH is more common in females, and males account for only 15% of cases.^[8] The disorder is widely believed to be an autoimmune disorder and is characterized by lymphocytic infiltration of the pituitary gland. Clinical manifestations are due to mass effects and variable degrees of hypopituitarism. While pituitary hormone deficiencies are common (80%), CDI is present in only 15% of the patient.^[9] Corticotrophs and thyrotrophs are more commonly affected than the other pituitary cells. Radiologically, the symmetrical sellar enlargement, stalk thickening, homogeneous enhancement following gadolinium administration, and “dural tail” sign help differentiate it from other sellar pathologies. The goals of treatment are to relieve pressure symptoms and replace deficient hormones.^[10] Our patient was a male and had LPH, the rarest form of LH.

TB of the pituitary gland, although extremely rare, is a cause of secondary granulomatous hypophysitis. Only a handful of cases have been reported in the literature, mainly from the developing countries and should be considered in the differential diagnosis of sellar mass in appropriate setting.^[11],[12] Tubercular hypophysitis is usually a part of systemic illness and results from hematogenous spread from the primary lesion elsewhere, like in our case. Clinical manifestations in tubercular hypophysitis are due to the mass effect of the enlarged pituitary, associated anterior and posterior pituitary hormone deficiencies, and systemic effect of the disease itself. Radiologically, it may be difficult to differentiate tubercular hypophysitis from other granulomatous lesions of the pituitary gland. Treatment includes antituberculous drugs, pituitary hormone replacement, and surgery when indicated.

Primary CNS lymphoma (PCNSL) accounts for approximately 2% of all intracranial neoplasms.^[13] PCNSL involving the hypothalamic-pituitary axis is extremely rare.^[14] It is usually seen in elderly population (>60 years). The symptoms are commonly related to mass effects and pituitary hormone deficiencies. Hypothalamic involvement can also result in eating disorders, temperature dysregulation, behavioral abnormalities, sleep disorders, autonomic dysfunction, and pituitary hormone deficiency including loss of AVP leading to CDI. Majority of the PCNSLs (98%) are B-cell non-Hodgkin lymphoma. Treatment includes chemotherapy and radiation targeting the lymphoma and appropriate hormone replacement therapy.^[15] Our patient was young and had hypothalamic involvement.

Permanent DI following pituitary surgery is a common complication. The incidence varies from 2% to 7%.^[16] It results from surgical injury to the hypothalamic magnocellular neurons. The risk factors for developing permanent DI following pituitary surgery include transcranial surgery, intraoperative CSF leak, patients of craniopharyngiomas, Rathke's cleft cyst, and Cushing's disease.^[17] In the immediate postoperative period, it has to be carefully distinguished from polyuria due to the physiological response to fluid overload and transient DI.

Conclusion

We report five cases of CDI with varied etiologies, some of which are very rare. CDI is a rare disorder of water-electrolyte homeostasis. It results from deficient secretion of AVP. The diagnosis of CDI and establishing the etiology is always a challenge for the physician. The correct diagnosis is of paramount importance for appropriate management. History, biochemical evaluation, and radiology combined may not always give the final answer. A definitive diagnosis may require tissue biopsy. Treatment includes surgery to relieve pressure symptoms, treatment of the underlying cause, and appropriate anterior and posterior pituitary hormone replacement.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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