Background
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. The term hypodipsia refers to a partial deficiency of the thirst mechanism. See the image below.
Anatomic relationships between pituitary and hypothalamic areas of interest with respect to regulation of antidiuretic hormone (ADH) secretion and thirst sensation. AN = Anterior (hypothalamic) nucleus; AP = Anterior pituitary; OC = optic chiasm; OVLT = Organum vasculosum of lamina terminalis; PA = Preoptic (hypothalamic) area; PP = Posterior pituitary; PVN = Paraventricular (hypothalamic) nucleus; SON = Supraoptic (hypothalamic) nucleus. Pathophysiology
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.[1]
In general, the threshold for AVP secretion is a small increase in serum osmolality from 280-290 mOsm/kg H 2 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 H 2 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).[2] 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. However, thirst serves as a back-up mechanism, thus freeing humans from frequently diverting attention towards water-seeking.
In rats, areas within the caudate nucleus appear to regulate water intake through norepinephrine-sensitive alpha receptors.[3] In a single case report in a dog, antithyroid antibodies led to hypothyroidism and adipsia, both of which resolved with levothyroxine therapy.[4] "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.[5]
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).[6, 7, 8] A constellation of adipsia, obesity, hyperprolactinemia, and hypothyroidism was reported in one child.[8]
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.
Epidemiology
Frequency
International
Adipsia is an extremely rare condition. Fewer than 100 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.[9]
Mortality/Morbidity
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.
Age
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.[10]
Verbalis JG, Berl T. Disorders of water balance. In: 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. Dec 2011;14(4):307-11. [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. Apr 2001;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. Jul 2007;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. Jan 2007;292(1):R112-23. [Medline].
Blank MS, Farnsworth PB. Idiopathic symptomatic hypernatremia in a 9-year-old boy: a clinical and physiologic evaluation. J Pediatr. Aug 1974;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. Dec 1976;89(6):898-903. [Medline].
Hayek A, Peake GT. Hypothalamic adipsia without demonstrable structural lesion. Pediatrics. Aug 1982;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. May 2008;51(5):851-9. [Medline].
Lopez-Capape M, Golmayo L, Lorenzo G, et al. Hypothalamic adipic hypernatraemia syndrome with normal osmoregulation of vasopressin. Eur J Pediatr. Oct 2004;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. Dec 1983;6(6):473-8. [Medline].
Bradley WG, Price DL. Adipsia in association with an arachnoid cyst. Neurology. Sep 1971;21(9):930-6. [Medline].
Christie SB, Ross EJ. Ectopic pinealoma with adipsia and hypernatraemia. Br Med J. Jun 15 1968;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. Nov 1974;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. Nov 3 1978;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. Apr 5 2003;152(14):436-8. [Medline].
Johnson AK, Buggy J. Periventricular preoptic-hypothalamus is vital for thirst and normal water economy. Am J Physiol. Mar 1978;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. Mar 1991;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. Oct 2004;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. Feb 1999;16:87-8. [Medline].
Mackay BM, Curtis N. Adipsia and hypernatraemia in a dog with focal hypothalamic granulomatous meningoencephalitis. Aust Vet J. Jan 1999;77(1):14-7. [Medline].
Papadimitriou A, Kipourou K, Manta C, et al. Adipsic hypernatremia syndrome in infancy. J Pediatr Endocrinol Metab. Sep-Oct 1997;10(5):547-50. [Medline].
Phillips MG, Gabow PA. Psychogenic adipsia in a patient with psychotic depression. Am J Kidney Dis. Jun 1990;15(6):592-4. [Medline].
Poll-The BT, Aicardi J. Pseudomonoventricle due to a malformation of the septum pellucidum. Neuropediatrics. Feb 1985;16(1):39-42. [Medline].
Robertson GL. Abnormalities of thirst regulation. Kidney Int. Feb 1984;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. Nov-Dec 1985;7(6):893-7. [Medline].
Schaad U, Vassella F, Zuppinger K, Oetliker O. Hypodipsia-hypernatremia syndrome. Helv Paediatr Acta. Feb 1979;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. Aug 1982;96(4):604-14. [Medline].
Silver BV, Stelly-Seitz C. Behavioral treatment of adipsia in a child with hypothalamic injury. Dev Med Child Neurol. Jun 1992;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. Jan 1981;52(1):9-16. [Medline].
Spiro SG, Jenkins JS. Adipsia and hypothermia after subarachnoid hemorrhage. Br Med J. Aug 14 1971;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. Jun 1967;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. Aug 1985;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. Jan 1987;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. Dec 1988;35(6):915-24. [Medline].
Print
