Adipsia is a disease characterized by the absence of thirst even in the presence of body water depletion or salt excess. It is a rare condition that typically presents as hypernatremic dehydration.  The cause is usually a hypothalamic lesion, which can be congenital or acquired. The term hypodipsia refers to a partial deficiency of the thirst mechanism. See the image below.
In humans, the thirst center is located in the anterior hypothalamus. The primary physiological stimuli for thirst are hypertonicity (osmotic) and hypovolemia. After infancy, an additional social stimulus for thirst is usually observed, which is viewed as secondary.
Osmoreceptors in the anterior wall of the third ventricle, near the organum vasculosum mediate the osmotic regulation of thirst, near to or even common to the osmoreceptors that regulate secretion of aqueous vasopressin (AVP). This stimulus is known as osmotic thirst. 
In general, the threshold for AVP secretion is a small increase in serum osmolality from 280-290 mOsm/kg H2 O. In contrast, the stimulus for osmotic thirst stimulation is set much higher, typically when near-maximal urine concentrations are achieved (ie, at serum osmolalities around 295 mOsm/Kg H2 O). The purpose of this dichotomy appears to be so that thirst can act as a back up mechanism, when pituitary and renal mechanisms are insufficient to keep plasma osmolality within a tight 1-2% range. If thirst were the primary system, humans would need to constantly divert attention towards seeking water.
After activation of osmotic thirst, downregulation of this stimulus occurs in 2 phases: (1) an immediate but short-lived downregulation of thirst by the oropharynx and upper GI tract and (2) a less immediate but more sustained downregulation by drop in serum osmolality (negative feedback).
Hypovolemia and hypotension may also stimulate thirst through the activation of low-pressure (venous) and high-pressure (arterial) vascular stretch receptors (hypovolemic thirst). Impulses from these receptors are transmitted by the vagus and the glossopharyngeal nerves to the medulla and from there to the hypothalamus. In addition, the hypothalamus is directly stimulated by angiotensin II. Such a hypovolemic thirst occurs with depletion of plasma volume by at least 4-8% in humans and 10-15% in some species.
Thirst abnormalities may result either from specific functional lesions that impair the activation of thirst by hypertonicity or hypovolemia or from generalized lesions that impair the cognitive processes required for thirst perception.
Any lesion, congenital or acquired, that affects the anterior hypothalamus may lead to the abolition of thirst. Because the center for AVP secretion occupies a contiguous area, lesions of the thirst center may also affect AVP (also known as antidiuretic hormone [ADH]) production, storage, or secretion), leading to impaired urinary concentrating ability. Therefore, patients may present with a combination of adipsia and central diabetes insipidus (ie, absence of AVP secretion), also known as adipsic diabetes insipidus. Such patients can develop severe hypernatremia, though it is chronic and therefore asymptomatic in many cases.  However, these patients have a much higher risk of infection and death.  . In adipsia, AVP secretion may be either completely unaffected, partially abolished, or completely abolished. In a normal situation, AVP acts along with thirst to maintain serum osmolality within tight control.
In rats, areas within the caudate nucleus appear to regulate water intake through norepinephrine-sensitive alpha receptors.  In a single case report in a dog, antithyroid antibodies led to hypothyroidism and adipsia, both of which resolved with levothyroxine therapy.  “Sickness behavior” is a condition in animals in which systemic infection leads to a highly regulated set of responses such as fever, anorexia, adipsia, inactivity, and cachexia. The neuroimmune communication may involve the interaction of cytokines with peripheral nerves.  In rat models, lipopolysaccharide is used to induce adipsia as part of sickness behavior. 
Although many different diseases can affect the anterior hypothalamus, adipsia is seen very infrequently even among patients with known anterior hypothalamic lesions. The reason adipsia is uncommon in such situations and the instances when adipsia is more likely to occur remain unknown.
Rarely, some children have adipsia without a definable structural lesion (essential adipsia). [9, 10, 11] A constellation of adipsia, obesity, hyperprolactinemia, and hypothyroidism was reported in one child. 
In hypodipsia, the exact pathological abnormalities are not known. AVP levels are normal, suggesting that neuronal pathways affecting thirst are selectively affected, either at the osmoreceptor level or further downstream.
Adipsia is an extremely rare condition. Fewer than 200 cases have been reported worldwide, although more cases are likely unreported. Mavrakis et al collated and described 70 reported cases in which thirst and AVP secretion were both abolished. 
Interestingly, a number of cases are reported in the veterinary literature, largely due to intracranial tumors, similar to causes in humans.
Adipsia leads to considerable difficulty in the management of water balance. Its common consequence is hypernatremic dehydration, which, when severe, is associated with hemodynamic and CNS manifestations. Adipsia has a higher morbidity than diabetes insipidus, in which the thirst mechanism is intact. 
Adipsia occurs in all age groups. Congenital malformations and traumatic lesions predominate in children, neoplastic lesions occur in all age groups, and psychogenic causes are more common in adults, particularly elderly persons. In children, adipsia without demonstrable structural lesions is very rare and has been reported in only 6-7 patients. 
Eisenberg Y, Frohman LA. ADIPSIC DIABETES INSIPIDUS: A REVIEW. Endocr Pract. 2016 Jan. 22 (1):76-83. [Medline].
Verbalis JG, Berl T. Disorders of water balance. Brenner BM. The Kidney. 8. WB Saunders; 2007. 8.
Sinha A, Ball S, Jenkins A, Hale J, Cheetham T. Objective assessment of thirst recovery in patients with adipsic diabetes insipidus. Pituitary. 2011 Dec. 14(4):307-11. [Medline].
Arima H, Wakabayashi T, Nagatani T, Fujii M, Hirakawa A, Murase T. Adipsia increases risk of death in patients with central diabetes insipidus. Endocr J. 2014. 61(2):143-8. [Medline].
Pal GK, Pal P, Raj SS, Mohan M. Modulation of feeding and drinking behaviour by catecholamines injected into nucleus caudatus in rats. Indian J Physiol Pharmacol. 2001 Apr. 45(2):172-80. [Medline].
Kang JH, Chang D, Lee YW, Na KJ, Yang MP. Adipsic hypernatremia in a dog with antithyroid antibodies in cerebrospinal fluid and serum. J Vet Med Sci. 2007 Jul. 69(7):751-4. [Medline].
Weiland TJ, Voudouris NJ, Kent S. CCK(2) receptor nullification attenuates lipopolysaccharide-induced sickness behavior. Am J Physiol Regul Integr Comp Physiol. 2007 Jan. 292(1):R112-23. [Medline].
Damm J, Harden LM, Gerstberger R, Roth J, Rummel C. The putative JAK-STAT inhibitor AG490 exacerbates LPS-fever, reduces sickness behavior, and alters the expression of pro- and anti-inflammatory genes in the rat brain. Neuropharmacology. 2013 Aug. 71:98-111. [Medline].
Blank MS, Farnsworth PB. Idiopathic symptomatic hypernatremia in a 9-year-old boy: a clinical and physiologic evaluation. J Pediatr. 1974 Aug. 85(2):215-9. [Medline].
Conley SB, Brocklebank JT, Taylor IT, Robson AM. Recurrent hypernatremia; a proposed mechanism in a patient with absence of thirst and abnormal excretion of water. J Pediatr. 1976 Dec. 89(6):898-903. [Medline].
Hayek A, Peake GT. Hypothalamic adipsia without demonstrable structural lesion. Pediatrics. 1982 Aug. 70(2):275-8. [Medline].
Mavrakis AN, Tritos NA. Diabetes insipidus with deficient thirst: report of a patient and review of the literature. Am J Kidney Dis. 2008 May. 51(5):851-9. [Medline].
Cuesta M, Hannon MJ, Thompson CJ. Adipsic diabetes insipidus in adult patients. Pituitary. 2017 Jun. 20 (3):372-380. [Medline].
Lopez-Capape M, Golmayo L, Lorenzo G, et al. Hypothalamic adipic hypernatraemia syndrome with normal osmoregulation of vasopressin. Eur J Pediatr. 2004 Oct. 163(10):580-3. [Medline].
[Guideline] Mentes JC. Hydration management. Iowa City (IA): University of Iowa Gerontological Nursing Interventions Research Center, Research Dissemination Core; 2004 Feb. [Full Text].
Booth JD, Josse RG, Singer W. Pituitary and hypothalamic dysfunction in a patient with a basal encephalocele. J Endocrinol Invest. 1983 Dec. 6(6):473-8. [Medline].
Bradley WG, Price DL. Adipsia in association with an arachnoid cyst. Neurology. 1971 Sep. 21(9):930-6. [Medline].
Christie SB, Ross EJ. Ectopic pinealoma with adipsia and hypernatraemia. Br Med J. 1968 Jun 15. 2(606):669-70. [Medline].
DeRubertis FR, Michelis MF, Davis BB. “Essential” hypernatremia. Report of three cases and review of the literature. Arch Intern Med. 1974 Nov. 134(5):889-95. [Medline].
Grossman SP, Dacey D, Halaris AE, et al. Aphagia and adipsia after preferential destruction of nerve cell bodies in hypothalamus. Science. 1978 Nov 3. 202(4367):537-9. [Medline].
Jeffery ND, Watson PJ, Abramson C, Notenboom A. Brain malformations associated with primary adipsia identified usingmagnetic resonance imaging. Vet Rec. 2003 Apr 5. 152(14):436-8. [Medline].
Johnson AK, Buggy J. Periventricular preoptic-hypothalamus is vital for thirst and normal water economy. Am J Physiol. 1978 Mar. 234(3):R122-9. [Medline].
Johnston S, Burgess J, McMillan T, Greenwood R. Management of adipsia by a behavioural modification technique. J Neurol Neurosurg Psychiatry. 1991 Mar. 54(3):272-4. [Medline].
Lopez-Capape M, Golmayo L, Lorenzo G, Gallego N, Barrio R. Hypothalamic adipic hypernatraemia syndrome with normal osmoregulation of vasopressin. Eur J Pediatr. 2004 Oct. 163(10):580-3. [Medline].
Macias Batista A, Martinez Martin FJ, de Pablos Velasco PL. [Diabetes insipidus and adipsic hypernatremia in a patient with a craniopharyngioma]. An Med Interna. 1999 Feb. 16:87-8. [Medline].
Mackay BM, Curtis N. Adipsia and hypernatraemia in a dog with focal hypothalamic granulomatous meningoencephalitis. Aust Vet J. 1999 Jan. 77(1):14-7. [Medline].
Papadimitriou A, Kipourou K, Manta C, et al. Adipsic hypernatremia syndrome in infancy. J Pediatr Endocrinol Metab. 1997 Sep-Oct. 10(5):547-50. [Medline].
Phillips MG, Gabow PA. Psychogenic adipsia in a patient with psychotic depression. Am J Kidney Dis. 1990 Jun. 15(6):592-4. [Medline].
Poll-The BT, Aicardi J. Pseudomonoventricle due to a malformation of the septum pellucidum. Neuropediatrics. 1985 Feb. 16(1):39-42. [Medline].
Robertson GL. Abnormalities of thirst regulation. Kidney Int. 1984 Feb. 25(2):460-9. [Medline].
Ronconi GF, Ronconi M, Stella M, et al. [Neurogenic hypernatremia with adipsia and cerebral malformations in a child with ectrodactyly-ectodermal dysplasia-cleft lip-palate syndrome]. Pediatr Med Chir. 1985 Nov-Dec. 7(6):893-7. [Medline].
Schaad U, Vassella F, Zuppinger K, Oetliker O. Hypodipsia-hypernatremia syndrome. Helv Paediatr Acta. 1979 Feb. 34(1):63-76. [Medline].
Schallert T. Adipsia produced by lateral hypothalamic lesions: facilitation of recovery by preoperative restriction of water intake. J Comp Physiol Psychol. 1982 Aug. 96(4):604-14. [Medline].
Silver BV, Stelly-Seitz C. Behavioral treatment of adipsia in a child with hypothalamic injury. Dev Med Child Neurol. 1992 Jun. 34(6):539-42. [Medline].
Sklar CA, Grumbach MM, Kaplan SL, Conte FA. Hormonal and metabolic abnormalities associated with central nervous system germinoma in children and adolescents and the effect of therapy: report of 10 patients. J Clin Endocrinol Metab. 1981 Jan. 52(1):9-16. [Medline].
Spiro SG, Jenkins JS. Adipsia and hypothermia after subarachnoid hemorrhage. Br Med J. 1971 Aug 14. 3(771):411-2. [Medline].
Travis LB, Dodge WF, Waggener JD, Kashemsant C. Defective thirst mechanism secondary to a hypothalamic lesion: studies in a child with adipsia, polyphagia, obesity, and persistent hyperosmolality. J Pediatr. 1967 Jun. 70(6):915-26. [Medline].
Verdin E, Smitz S, Thibaut A, et al. Adipsic hypernatremia in a patient with pseudotumor cerebri and the primary empty sella syndrome. J Endocrinol Invest. 1985 Aug. 8(4):369-72. [Medline].
Villadsen AB, Pedersen EB. Recumbent cranial diabetes insipidus. Studies in a patient with adipsia, hypernatremia, poikilothermia and polyphagia. Acta Paediatr Scand. 1987 Jan. 76(1):179-83. [Medline].
Yamamoto T, Shimizu M, Fukuyama J, Yamaji T. Pathogenesis of extracellular fluid abnormalities of hypothalamic hypodipsia-hypernatremia syndrome. Endocrinol Jpn. 1988 Dec. 35(6):915-24. [Medline].
Crowley RK, Sherlock M, Agha A, Smith D, Thompson CJ. Clinical insights into adipsic diabetes insipidus: a large case series. Clin Endocrinol (Oxf). 2007 Apr. 66(4):475-82. [Medline].
Vikas R Dharnidharka, MD, MPH Professor and Chief, Division of Pediatric Nephrology, Hypertension and Pheresis, St Louis Children’s Hospital, Washington University in St Louis School of Medicine
Vikas R Dharnidharka, MD, MPH is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, American Society of Pediatric Nephrology, American Society of Transplantation
Disclosure: Received consulting fee from Atara Biotherapeutics and Bristol-Myers-Squibb for consulting; Received grant/research funds from Bristol-Myers-Squibb, Novartis for site PI on study. Received honoraria from Sanofi. .
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Adrian Spitzer, MD Clinical Professor Emeritus, Department of Pediatrics, Albert Einstein College of Medicine
Adrian Spitzer, MD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Pediatric Society, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, Society for Pediatric Research
Disclosure: Nothing to disclose.
Craig B Langman, MD The Isaac A Abt, MD, Professor of Kidney Diseases, Northwestern University, The Feinberg School of Medicine; Division Head of Kidney Diseases, The Ann and Robert H Lurie Children’s Hospital of Chicago
Disclosure: Received income in an amount equal to or greater than $250 from: Alexion Pharmaceuticals; Horizon Pharmaceuticals); ; Dicerna, Jannsen Pharmaceuticals.
Uri S Alon, MD Director of Bone and Mineral Disorders Clinic and Renal Research Laboratory, Children’s Mercy Hospital of Kansas City; Professor, Department of Pediatrics, Division of Pediatric Nephrology, University of Missouri-Kansas City School of Medicine
Uri S Alon, MD is a member of the following medical societies: American Federation for Medical Research
Disclosure: Nothing to disclose.
Research & References of Adipsia|A&C Accounting And Tax Services