Episodic spontaneous hypothermia is an infrequent disorder, the pathogenic mechanisms of which have not been completely clarified, although alterations in the serotoninergic system have been suggested. We report the history of a girl with episodes of dizziness and shivering associated with a body temperature lower than 35°C since the age of 10 months. At the age of 11 years, she was admitted to a local hospital and an oral glucose tolerance test showed high total insulin levels. Hypoglycemia secondary to hyperinsulinemia was suspected, and a low-carbohydrate (simple) diet was proposed without results. Due to the recurrence of the episodes, episodic spontaneous hypothermia triggered by hyperinsulinemia was suspected, and treatment with flunarizine, a drug considered the first line in the treatment of migraine-related disorders, was started with a resulting reduction in the episodes. A new endocrinological evaluation showed decreased insulin secretion. In our patient, the success of the therapy might be due to the well-known effect of calcium antagonists in inhibiting serotonin uptake and thereby regulating serotonin levels after hyperinsulinism. This case suggests hyperinsulinemia as a potential mechanism for episodic spontaneous hypothermia, probably mediated by an interaction between insulin and the serotoninergic system.

1.
Arav-Boger R, Spirer Z: Periodic syndromes of childhood. Adv Pediatr 1997;44:389–428.
2.
Sheth RD, Barron TF, Harlage PL: Episodic spontaneous hypothermia with hyperhidrosis: implication for pathogenesis. Pediatr Neurol 1994;10:58–60.
3.
Shapiro WR, Williams GTT, Plum F: Spontaneous recurrent hypothermia accompanying agenesis of the corpus callosum. Brain 1969;92:423–426.
4.
Ruiz C, Gener B, Garaizar C, Prats JM: Episodic spontaneous hypothermia: a periodic childhood syndrome. Pediatr Neurol 2003;28:304–306.
5.
Arroyo HA, Di Blasi M, Fejerman N: Episodic spontaneous hypothermia with hyperhidrosis. Pediatr Neurol 1994;11:266.
6.
Bosacki C, Hausfater P, Koenig M, Serratrice J, Piette AM, Cathebras P: Spontaneous hypothermia: a series of ten cases, place of Shapiro’s syndrome (article in French). Rev Med Interne 2005;26:615–623.
7.
Greenberg RA, Rittichier KK: Pediatric nonenviromental hypothermia presenting to the emergency department: episodic spontaneous hypothermia with hyperhidrosis. Pediatr Emerg Care 2003;19:32–34.
8.
Arroyo HA, Di Blasi M, Grinszpan G: A syndrome of hyperhidrosis, hypothermia, and bradycardia possibly due to central monoaminergic dysfunction. Neurology 1990;40:556–557.
9.
Orosco M, Rouch C, Gerozissis K: Activation of hypothalamic insulin by serotonin is the primary event of the insulin-serotonin interaction involved in the control of feeding. Brain Res 2000;872:64–70.
10.
Lechin F, Van der Dijs B: Central nervous system circuitry involved in the hyperinsulinism syndrome. Neuroendocrinology 2006;84:222–234.
11.
Telib M, Raptis S, Schroeder KE, Pfeiffer EF: Serotonin and insulin release in vitro. Diabetologia 1968;4:253–256.
12.
Rouch C, Nicolaidis S, Orosco M: Determination, using microdialysis, of hypothalamic serotonin variations in response to different macronutrients. Physiol Behav 1999;65:653–657.
13.
Lechin F, Van de Djis B, Lechin A, Coll-Garcia E, Jara H, Cabrera A, Jimines V, Gomez F, Tovar D: Doxepin therapy for postprandial symptomatic hypoglycaemic patients: neurochemical hormonal and metabolic disturbances. Clin Sci 1991;80:373–384.
14.
Wozniak M, Rydzewski B, Baker SP, Raizada MK: The cellular and physiological actions of insulin in the central nervous system. Neurochem Int 1993;22:1–10.
15.
Evers S, Pothmann R, Uberall M, Naumann E, Gerber WD: Treatment of idiopathic headache in childhood – recommendations of the German Migraine and Headache Society (DMKG). Schmerz 2002;16:48–56.
16.
Pukhal’skaya TG, Kolosova OA, Men’shikov MY, Vein AM: Effects of calcium antagonists on serotonin-dependent aggregation and serotonin transport in platelets of patients with migraine. Bull Exp Biol Med 2000;130:633–635.
17.
Capellà D, Laporte JR, Castel JM, Tristan C, Cos A, Morales-Olivas FJ: Parkinsonism, tremor, and depression induced by cinnarazine and flunarizine. BMJ 1988;297:722–723.
18.
Micheli FE, Pardal MM, Giannaula R, Gatto M, Parera I, Paradiso G, Torres M, Pikielny R, Pardal J: Movement disorders and depression due to flunarizine and cinnarizine. Mov Disord 1989;4:139–146.
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