Seasonal Thrombocytopenia Induced by Hypothalamic Hypothermia: A Case Report

Seasonal Thrombocytopenia Induced by Hypothalamic Hypothermia: A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Seasonal Thrombocytopenia Induced by Hypothalamic Hypothermia: A Case Report Masahiro Tanji, Noritaka Sano, Hiroyuki Ikeda, Kan Sumita, Etsuko Yamamoto Hattori, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6591159/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background The hypothalamus plays a central role in thermoregulation. In brain tumors involving the hypothalamus, hypothermia can lead to rare but serious complications such as impaired consciousness and thrombocytopenia. Case Presentation An 80-year-old man was brought to our hospital in February after being found unresponsive in his bedroom. He had a history of surgery for a giant PitNET at another institution and was subsequently followed at our hospital. Having declined further surgical intervention, he was managed conservatively. During follow-up, episodes of unexplained paroxysmal thrombocytopenia were occasionally observed. Upon arrival, he was comatose with a core body temperature of 32.1°C. Laboratory tests revealed marked thrombocytopenia (55,000/µL) and widespread subcutaneous hemorrhages. Hypothermia was considered the primary cause of the impaired consciousness. Because the patient’s body temperature was gradually normalized by external warming, his level of consciousness improved, and his platelet count also began to recover over the following days. A retrospective review of prior laboratory data revealed a seasonal pattern in the thrombocytopenia. Based on these findings, the thrombocytopenia was considered secondary to hypothalamic hypothermia. Conclusions Hypothalamic tumors can precipitate hypothermia and seasonal hematologic disturbances. In patients with brain tumors presenting with unexplained, seasonal, or periodic thrombocytopenia, underlying thermoregulatory dysfunction due to hypothalamic involvement should be considered. hypothermia hypothalamus thrombocytopenia pituitary neuroendocrine tumor case report Figures Figure 1 Figure 2 Figure 3 Background The hypothalamus plays a key role in maintaining homeostasis by sensing changes in core body temperature [ 1 ]. Maintaining an appropriate core temperature is essential for optimal cellular and systemic function. Brain tumors located near the hypothalamus (e.g., craniopharyngiomas) or those that directly invade the hypothalamus can result in hypothalamic injury. However, there have been few reports of brain tumors associated with hypothalamic hypothermia. Hypothermia can lead to various systemic effects, including bradycardia and thrombocytopenia [ 2 ], but it remains a rare and often underdiagnosed condition that poses significant challenges for timely recognition and management. We herein report a case involving a patient with a giant pituitary neuroendocrine tumor (PitNET) who exhibited seasonal thrombocytopenia during outpatient follow-up and was later admitted to the emergency department in winter with impaired consciousness due to severe hypothermia. Case presentation History An 80-year-old man was admitted to the hospital in February with impaired consciousness after being found unresponsive in his bedroom. He had a known history of a giant PitNET associated with bilateral hemianopsia. Twelve years earlier, he had undergone partial resection of the tumor at another hospital; complete removal was not possible because of its firmness. Following the surgery, transient thrombocytopenia was observed, prompting a referral to hematology, where myelodysplastic syndrome was suspected. However, bone marrow biopsy findings were inconclusive. Two years later, he was referred to our hospital, but he declined further surgical intervention and was managed conservatively with regular follow-up. Over time, the lesion gradually increased in size, and magnetic resonance imaging showed compression of the anterior portion of the left hypothalamus (Fig. 1 ). Periodically, blood tests revealed recurrent thrombocytopenia of unknown origin. Because the platelet count spontaneously recovered during follow-up and no bleeding episodes occurred, no further hematologic investigations were pursued. He had been on hormone replacement therapy for panhypopituitarism. On arrival, he was comatose with a Glasgow Coma Scale score of E2V1M1. His blood pressure was 114/89 mmHg, and his heart rate was 58 bpm. Brain magnetic resonance imaging revealed no acute abnormalities. However, his core body temperature was 32.1°C, indicating profound hypothermia. Laboratory data showed marked thrombocytopenia, with a platelet count of 55,000/µL, and multiple subcutaneous hemorrhages were noted (Fig. 2 ). Suspecting hypothermia as the cause of his altered mental status, we initiated external rewarming along with steroid administration. His body temperature reached 36.1°C within 24 hours of admission. His level of consciousness gradually improved, reaching a Glasgow Coma Scale score of E3V4M6 after several days. His platelet count also showed gradual recovery: on the seventh day, it was 111,000/µL, and by the ninth day, it had increased to 167,000/µL. Because of reduced activities of daily living resulting from aspiration pneumonia during the resumption of oral intake, the patient was transferred to a rehabilitation hospital. Correlation between average monthly temperature and platelet count The Japan Meteorological Agency provides data on the average monthly temperature in the patient’s prefecture of residence [ 3 ]. The monthly distribution of platelet counts over a 10-year period demonstrated a clear seasonal pattern, with lower values consistently observed during the winter months (January–February) and higher values in the summer (July–September) (Fig. 3 A). To further investigate the relationship between platelet counts and ambient temperature, the patient’s historical platelet data over the 10-year period were compared with corresponding monthly average temperatures. The scatter plot illustrates this relationship (Fig. 3 B), showing a very strong positive correlation (Pearson’s r = 0.819), indicating that higher temperatures are associated with elevated platelet levels. Data analysis was performed using Microsoft Excel for Mac, version 16.95.1. Discussion and Conclusions This patient presented with two particularly noteworthy features. First, hypothermia-induced coma resulting from hypothalamic damage caused by a PitNET is extremely rare. Second, thrombocytopenia with seasonal fluctuations has not been well defined. Because these complications are highly uncommon in the context of PitNET, the etiology of the paroxysmal thrombocytopenia remained unclear in the outpatient clinic until the onset of hypothermia-induced impaired consciousness. Hypothermia is defined as a condition in which the body’s thermoregulatory mechanisms are overwhelmed, resulting in a decrease in core body temperature to ≤ 35°C. In homeothermic animals, central regulation of body temperature is mediated by a neural pathway involving the upper preoptic area of the hypothalamus [ 1 ]. In a mouse model, neurons in the upper preoptic cortex suppress excitatory sympathetic output from the dorsomedial hypothalamus to the medullary raphe nucleus. By modulating the degree of this inhibition, the system maintains thermal homeostasis. When ambient temperatures are high, increased inhibitory signaling enhances heat dissipation and prevents hyperthermia. Conversely, during cold exposure or infection, inhibition is reduced, leading to enhanced sympathetic output, increased heat production, and the prevention of hypothermia or induction of fever [ 4 ]. In human case studies, impaired thermoregulation due to hypothalamic dysfunction has been reported in various conditions. For example, traumatic injury to the hypothalamus following traffic accidents has been associated with disordered thermoregulation [ 5 ]. Iatrogenic cases have also been documented, including thermoregulatory dysfunction following third ventricular fenestration [ 6 ], and transient hypothermia after basilar artery clipping via the third ventricle [ 7 ]. With regard to brain tumors, several reports describe thermoregulatory disturbances in craniopharyngiomas [ 2 , 8 – 10 ] and hypothalamic astrocytoma [ 11 ]. Other etiologies include hypothalamic dysfunction secondary to tuberculous meningitis [ 12 ]. Hypothermia accompanied by thrombocytopenia has also been reported in patients with multiple sclerosis [ 13 ]. More recently, although rare, some studies have suggested an association between hypothalamic thermoregulatory disturbance and epilepsy [ 14 , 15 ]. In the field of forensic medicine, cases of hypothermia resulting from hypothalamic lesions have been identified during autopsies of individuals who died of unknown causes. These reports include cases involving glioblastoma multiforme [ 16 ] and pituitary adenoma [ 17 , 18 ]. Such findings underscore the importance of recognizing that hypothermia due to hypothalamic damage can be fatal in some cases. Although there was no formal documentation of seasonal fluctuations in body temperature during hospital visits, the patient’s family reported that his body temperature tended to be lower during the winter months, suggesting the presence of seasonal variation. Erlich-Malona et al. [ 19 ] described two postoperative brain tumor patients—one with a pituitary adenoma and the other with a pilocytic astrocytoma—who developed paroxysmal hypothermia, and the authors proposed a diagnostic algorithm and scoring tool for its assessment. Based on their criteria, our case appears to correspond to a highly likely diagnosis of paroxysmal hypothermia. In this case, the patient exhibited seasonal and periodic pancytopenia, particularly thrombocytopenia. Myelodysplastic syndrome had been suspected at a previous hospital, and a bone marrow biopsy was performed; however, the findings were within normal limits. Initially, the seasonal pattern was not recognized, and the degree of thrombocytopenia was relatively mild; therefore, the patient was followed without intervention. During the current episode, the patient experienced hypothermia severe enough to cause impaired consciousness. At the time of emergency transport, the platelet count was at its lowest recorded level, and the ambient temperature on that day was also significantly low. This prompted us to consider the possibility of seasonal thrombocytopenia related to a thermoregulatory disorder. Because the patient had undergone regular blood sampling, we analyzed the correlation between platelet counts and the average monthly temperature in the patient’s prefecture of residence. A clear seasonal trend was observed, with lower platelet counts during the winter months (January–February) and higher values in the summer (July–September) (Fig. 3 A). In addition, a strong positive correlation between temperature and platelet count was identified (Pearson’s r = 0.819) (Fig. 3 B). Thrombocytopenia associated with hypothermia has been classically documented in the context of cardiac bypass surgery performed under hypothermic conditions. Animal studies, such as those conducted in dogs, have demonstrated platelet sequestration in the spleen and liver under hypothermic conditions [ 20 , 21 ]. Using radiolabeled platelets, these studies identified the liver—possibly in combination with the spleen—as the primary site of platelet sequestration. Notably, the thrombocytopenia observed in these models was reversible upon rewarming. Interestingly, platelet dynamics during hibernation in hamsters also involve temporary storage and subsequent release, likely due to margination along the vessel walls in liver sinusoids [ 22 ]. In the setting of chronic hypothermia, however, additional mechanisms may be involved. In such cases, not only sequestration but also impaired platelet production must be considered [ 23 ]. There are sporadic reports of pancytopenia attributed to reduced bone marrow activity [ 2 ]. Moreover, platelet function itself may be impaired during hypothermia [ 24 ]. Hypothermia inhibits upregulation of granule membrane protein-140, downregulates the glycoprotein Ib-IX complex, suppresses platelet aggregation, and reduces production of thromboxane B 2 (a stable metabolite of thromboxane A 2 ) in vitro . All of these inhibitory effects are fully reversed upon rewarming the blood to 37°C. Although it remains unclear whether the thrombocytopenia in our patient was primarily due to platelet sequestration, impaired production, or platelet malfunction, he presented with widespread subcutaneous hemorrhages on admission. His platelet count recovered rapidly within a few days of supportive care and rewarming, suggesting a reversible process likely influenced by hypothermia. In summary, it is important to recognize that underlying thermoregulatory dysfunction may be present in patients with large PitNETs and unexplained seasonal or periodic thrombocytopenia. Such thermoregulatory dysfunction can occasionally lead to serious complications, including impaired consciousness. Therefore, appropriate precautions regarding temperature management should be taken in collaboration with the patient and their family. Abbreviations PitNET pituitary neuroendocrine tumor Declarations Acknowledgments We would like to thank the co-medical staff at Kyoto University Hospital for their support in the neurocritical care of this patient. We also thank Angela Morben, DVM, ELS, from Edanz (https://jp.edanz.com/ac), for editing a draft of this manuscript. Authors’ contributions MT and KS were involved in patient data collection. MT, NS and HI performed the data analysis. YM contributed to the interpretation of results. MT drafted the manuscript, with critical input and revisions from NS, EYH, ST and YM. The manuscript was reviewed for intellectual content by CS and YA. All authors read and approved the final version of the manuscript. Funding The authors declare that they have no source of funding. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate Informed consent was obtained from all patients. This report was approved by the institutional ethics committee (R2088). Consent for publication Written informed consent for publication of the case report and accompanying images was obtained from the patient and his legal guardians. Competing interests The authors declare no conflicts of interest. References Morrison SF, Nakamura K. Central mechanisms for thermoregulation. Annu Rev Physiol. 2019;81:285-308. doi:10.1146/annurev-physiol-020518-114546 de Vetten L, Bocca G. Systemic effects of hypothermia due to hypothalamic dysfunction after resection of a craniopharyngioma: case report and review of literature. Neuropediatrics. 2013;44:159-62. doi:10.1055/s-0032-1327773. Japan Meteorological Agency. Monthly climate statistics. https://www.data.jma.go.jp/stats/etrn/view/monthly_s3.php?prec_no=61&block_no=47759. Accessed [20 Apr 2025]. Nakamura Y, Yahiro T, Fukushima A, Kataoka N, Hioki H, Nakamura K. Prostaglandin EP3 receptor-expressing preoptic neurons bidirectionally control body temperature via tonic GABAergic signaling. Sci Adv. 2022;8:eadd5463. doi:10.1126/sciadv.add5463 Ratcliffe PJ, Bell JI, Collins KJ, Frackowiak RS, Rudge P. Late onset post-traumatic hypothalamic hypothermia. J Neurol Neurosurg Psychiatry. 1983;46:72-4. doi:10.1136/jnnp.46.1.72 Moreira Marques T, Almeida A, Pinheiro J, Nascimento PO. Dysautonomia secondary to third ventriculostomy successfully managed with midodrine. BMJ Case Rep. 2020;13:e232767. doi:10.1136/bcr-2019-232767 Hidaka T, Ikawa F, Hamasaki O, Kurokawa Y, Yonezawa U, Kurisu K. A case of transient hypothermia after trans-lamina terminalis and third ventricle clipping of an extremely high-position basilar tip aneurysm. SAGE Open Med Case Rep. 2015;3:2050313X15578318. doi:10.1177/2050313X15578318 Griffiths AP, Henderson M, Penn ND, Tindall H. Haematological, neurological and psychiatric complications of chronic hypothermia following surgery for craniopharyngioma. Postgrad Med J. 1988;64:617-20. doi:10.1136/pgmj.64.754.617 Erfurth EM, Holmer H, Fjalldal SB. Mortality and morbidity in adult craniopharyngioma. Pituitary. 2013;16:46-55. doi:10.1007/s11102-012-0428-2 Galbiati F, Stamatiades GA, Bi WL, Abreu AP. Hypothalamic and pituitary dysfunction after extensive brain surgery: there is thirst for more knowledge. JCEM Case Rep. 2023;1:luad137. doi:10.1210/jcemcr/luad137 Haugh RM, Markesbery WR. Hypothalamic astrocytoma. Syndrome of hyperphagia, obesity, and disturbances of behavior and endocrine and autonomic function. Arch Neurol. 1983;40:560-3. doi:10.1001/archneur.1983.04050080060011 Joshi VV, Chaudhuri A, Karnad DR, Tilve GH. Hypothermia due to transient hypothalamic dysfunction in tuberculous meningitis with hydrocephalus. Br J Neurosurg. 1992;6:385-7. doi:10.3109/02688699209023801 Toledano M, Weinshenker BG, Kaufmann TJ, Parisi JE, Paz Soldán MM. Demographics and clinical characteristics of episodic hypothermia in multiple sclerosis. Mult Scler. 2019;25:709-14. doi:10.1177/1352458518767045 Devic P, Peter-Derex L, Richard-Mornas A, Ernesto S, Nesme P, Mauguière F, et al. Late-onset post-lesional paroxysmal hypothermia: a case series and literature review. J Neurol. 2020;267:3301-9. doi:10.1007/s00415-020-10013-3 Rossignon P, El Alaoui K, Soupart A. Spontaneous periodic hypothermia with confirmed epilepsy: a report of two cases. Eur J Case Rep Intern Med. 2023;10:003960. doi:10.12890/2023_003960 Morgan M, Schwartz L, Duflou J. Hypothermia secondary to glioblastoma multiforme? Autopsy findings in two cases. J Forensic Sci. 2015;60:511-3. doi:10.1111/1556-4029.12699 Ward ME, Cowley AR. Hypothermia: a natural cause of death. Am J Forensic Med Pathol. 1999;20:383-6. doi:10.1097/00000433-199912000-00014 Suzuki H, Hayashi K, Fukunaga T. Two forensic autopsy cases of death from unexpected lesions of the pituitary gland. Leg Med (Tokyo). 2014;16:36-9. doi:10.1016/j.legalmed.2013.10.004 Erlich-Malona N, Bartolini L, D'Abreu A, Roth J. Paroxysmal hypothermia with prominent parkinsonian features after suprachiasmatic tumor resection. Neurohospitalist. 2022;12:285-9. doi:10.1177/19418744211056206 Villalobos TJ, Adelson E, Riley PA Jr, Crosby WH. A cause of the thrombocytopenia and leukopenia that occur in dogs during deep hypothermia. J Clin Invest. 1958;37:1-7. doi:10.1172/JCI103576 Hessel EA 2nd, Schmer G, Dillard DH. Platelet kinetics during deep hypothermia. J Surg Res. 1980;28:23-34. doi:10.1016/0022-4804(80)90078-5 de Vrij EL, Bouma HR, Goris M, Weerman U, de Groot AP, Kuipers J, et al. Reversible thrombocytopenia during hibernation originates from storage and release of platelets in liver sinusoids. J Comp Physiol B. 2021;191:603-15. doi:10.1007/s00360-021-01351-3 O'Brien H, Amess JA, Mollin DL. Recurrent thrombocytopenia, erythroid hypoplasia and sideroblastic anaemia associated with hypothermia. Br J Haematol. 1982;51:451-6. Michelson AD, MacGregor H, Barnard MR, Kestin AS, Rohrer MJ, Valeri CR. Reversible inhibition of human platelet activation by hypothermia in vivo and in vitro. Thromb Haemost. 1994;71:633-40. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 17 Jun, 2025 Reviewers agreed at journal 15 Jun, 2025 Reviews received at journal 13 Jun, 2025 Reviewers agreed at journal 13 Jun, 2025 Reviewers invited by journal 13 Jun, 2025 Editor assigned by journal 11 Jun, 2025 Editor invited by journal 21 May, 2025 Submission checks completed at journal 20 May, 2025 First submitted to journal 20 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6591159","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":471491669,"identity":"7f7741c6-dba2-4fd3-8cf4-151225cfaae0","order_by":0,"name":"Masahiro 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resonance imaging of the patient\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eT2-weighted images demonstrate a tumor (asterisk) compressing the anterior portion of the left hypothalamus (yellow arrow). \u003cstrong\u003eA:\u003c/strong\u003eCoronal view. \u003cstrong\u003eB:\u003c/strong\u003e Axial view.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6591159/v1/f319d19a26a0bd96f789caf9.png"},{"id":84858633,"identity":"7be681a7-6484-4eb1-a5a4-7242774ff3c8","added_by":"auto","created_at":"2025-06-18 06:35:52","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":675512,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eClinical photographs showing multiple purpuric lesions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA:\u003c/strong\u003e Multiple small subcutaneous hemorrhages observed on the trunk. \u003cstrong\u003eB:\u003c/strong\u003e A large subcutaneous hemorrhage observed on the patient’s back.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6591159/v1/84ef2903264a6e364a34825e.png"},{"id":84858637,"identity":"15f7574f-84fd-4acb-bf35-bca85970ea11","added_by":"auto","created_at":"2025-06-18 06:35:52","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":161357,"visible":true,"origin":"","legend":"\u003cp\u003eAnalysis of relationship between platelet counts and temperature\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA:\u003c/strong\u003e Dual-axis time-series plot showing monthly changes in platelet count (left axis, orange line) and ambient temperature (right axis, blue line) from 2015 to 2025. Ambient temperature data were available for all months, whereas platelet count values were intermittently missing. Missing values were not imputed; instead, observed data points were connected with lines to preserve the temporal pattern without interpolation. Both platelet counts and ambient temperatures exhibited cyclical trends, with nadirs typically observed in winter and peaks in summer. \u003cstrong\u003eB:\u003c/strong\u003e Scatter plots showing the relationship between monthly average temperature and platelet count, with a fitted linear regression line. A strong positive correlation was observed (Pearson’s \u003cem\u003er\u003c/em\u003e = 0.819).\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-6591159/v1/be4f230440dd63754a40f299.png"},{"id":84860463,"identity":"bc5e59a7-9ea4-4eab-95b0-4344d8b249e6","added_by":"auto","created_at":"2025-06-18 06:51:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2499756,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6591159/v1/500702a2-0026-4437-bd3d-b39c1516f1eb.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Seasonal Thrombocytopenia Induced by Hypothalamic Hypothermia: A Case Report","fulltext":[{"header":"Background","content":"\u003cp\u003eThe hypothalamus plays a key role in maintaining homeostasis by sensing changes in core body temperature [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Maintaining an appropriate core temperature is essential for optimal cellular and systemic function.\u003c/p\u003e \u003cp\u003eBrain tumors located near the hypothalamus (e.g., craniopharyngiomas) or those that directly invade the hypothalamus can result in hypothalamic injury. However, there have been few reports of brain tumors associated with hypothalamic hypothermia. Hypothermia can lead to various systemic effects, including bradycardia and thrombocytopenia [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], but it remains a rare and often underdiagnosed condition that poses significant challenges for timely recognition and management.\u003c/p\u003e \u003cp\u003eWe herein report a case involving a patient with a giant pituitary neuroendocrine tumor (PitNET) who exhibited seasonal thrombocytopenia during outpatient follow-up and was later admitted to the emergency department in winter with impaired consciousness due to severe hypothermia.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eHistory\u003c/h2\u003e \u003cp\u003eAn 80-year-old man was admitted to the hospital in February with impaired consciousness after being found unresponsive in his bedroom. He had a known history of a giant PitNET associated with bilateral hemianopsia. Twelve years earlier, he had undergone partial resection of the tumor at another hospital; complete removal was not possible because of its firmness. Following the surgery, transient thrombocytopenia was observed, prompting a referral to hematology, where myelodysplastic syndrome was suspected. However, bone marrow biopsy findings were inconclusive. Two years later, he was referred to our hospital, but he declined further surgical intervention and was managed conservatively with regular follow-up. Over time, the lesion gradually increased in size, and magnetic resonance imaging showed compression of the anterior portion of the left hypothalamus (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Periodically, blood tests revealed recurrent thrombocytopenia of unknown origin. Because the platelet count spontaneously recovered during follow-up and no bleeding episodes occurred, no further hematologic investigations were pursued. He had been on hormone replacement therapy for panhypopituitarism.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOn arrival, he was comatose with a Glasgow Coma Scale score of E2V1M1. His blood pressure was 114/89 mmHg, and his heart rate was 58 bpm. Brain magnetic resonance imaging revealed no acute abnormalities. However, his core body temperature was 32.1\u0026deg;C, indicating profound hypothermia. Laboratory data showed marked thrombocytopenia, with a platelet count of 55,000/\u0026micro;L, and multiple subcutaneous hemorrhages were noted (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSuspecting hypothermia as the cause of his altered mental status, we initiated external rewarming along with steroid administration. His body temperature reached 36.1\u0026deg;C within 24 hours of admission. His level of consciousness gradually improved, reaching a Glasgow Coma Scale score of E3V4M6 after several days. His platelet count also showed gradual recovery: on the seventh day, it was 111,000/\u0026micro;L, and by the ninth day, it had increased to 167,000/\u0026micro;L. Because of reduced activities of daily living resulting from aspiration pneumonia during the resumption of oral intake, the patient was transferred to a rehabilitation hospital.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCorrelation between average monthly temperature and platelet count\u003c/h3\u003e\n\u003cp\u003eThe Japan Meteorological Agency provides data on the average monthly temperature in the patient\u0026rsquo;s prefecture of residence [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The monthly distribution of platelet counts over a 10-year period demonstrated a clear seasonal pattern, with lower values consistently observed during the winter months (January\u0026ndash;February) and higher values in the summer (July\u0026ndash;September) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). To further investigate the relationship between platelet counts and ambient temperature, the patient\u0026rsquo;s historical platelet data over the 10-year period were compared with corresponding monthly average temperatures. The scatter plot illustrates this relationship (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB), showing a very strong positive correlation (Pearson\u0026rsquo;s \u003cem\u003er\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.819), indicating that higher temperatures are associated with elevated platelet levels. Data analysis was performed using Microsoft Excel for Mac, version 16.95.1.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion and Conclusions","content":"\u003cp\u003eThis patient presented with two particularly noteworthy features. First, hypothermia-induced coma resulting from hypothalamic damage caused by a PitNET is extremely rare. Second, thrombocytopenia with seasonal fluctuations has not been well defined. Because these complications are highly uncommon in the context of PitNET, the etiology of the paroxysmal thrombocytopenia remained unclear in the outpatient clinic until the onset of hypothermia-induced impaired consciousness.\u003c/p\u003e \u003cp\u003eHypothermia is defined as a condition in which the body\u0026rsquo;s thermoregulatory mechanisms are overwhelmed, resulting in a decrease in core body temperature to \u0026le;\u0026thinsp;35\u0026deg;C. In homeothermic animals, central regulation of body temperature is mediated by a neural pathway involving the upper preoptic area of the hypothalamus [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In a mouse model, neurons in the upper preoptic cortex suppress excitatory sympathetic output from the dorsomedial hypothalamus to the medullary raphe nucleus. By modulating the degree of this inhibition, the system maintains thermal homeostasis. When ambient temperatures are high, increased inhibitory signaling enhances heat dissipation and prevents hyperthermia. Conversely, during cold exposure or infection, inhibition is reduced, leading to enhanced sympathetic output, increased heat production, and the prevention of hypothermia or induction of fever [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In human case studies, impaired thermoregulation due to hypothalamic dysfunction has been reported in various conditions. For example, traumatic injury to the hypothalamus following traffic accidents has been associated with disordered thermoregulation [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Iatrogenic cases have also been documented, including thermoregulatory dysfunction following third ventricular fenestration [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], and transient hypothermia after basilar artery clipping via the third ventricle [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. With regard to brain tumors, several reports describe thermoregulatory disturbances in craniopharyngiomas [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and hypothalamic astrocytoma [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Other etiologies include hypothalamic dysfunction secondary to tuberculous meningitis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Hypothermia accompanied by thrombocytopenia has also been reported in patients with multiple sclerosis [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. More recently, although rare, some studies have suggested an association between hypothalamic thermoregulatory disturbance and epilepsy [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the field of forensic medicine, cases of hypothermia resulting from hypothalamic lesions have been identified during autopsies of individuals who died of unknown causes. These reports include cases involving glioblastoma multiforme [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] and pituitary adenoma [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Such findings underscore the importance of recognizing that hypothermia due to hypothalamic damage can be fatal in some cases.\u003c/p\u003e \u003cp\u003eAlthough there was no formal documentation of seasonal fluctuations in body temperature during hospital visits, the patient\u0026rsquo;s family reported that his body temperature tended to be lower during the winter months, suggesting the presence of seasonal variation. Erlich-Malona et al. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] described two postoperative brain tumor patients\u0026mdash;one with a pituitary adenoma and the other with a pilocytic astrocytoma\u0026mdash;who developed paroxysmal hypothermia, and the authors proposed a diagnostic algorithm and scoring tool for its assessment. Based on their criteria, our case appears to correspond to a highly likely diagnosis of paroxysmal hypothermia.\u003c/p\u003e \u003cp\u003eIn this case, the patient exhibited seasonal and periodic pancytopenia, particularly thrombocytopenia. Myelodysplastic syndrome had been suspected at a previous hospital, and a bone marrow biopsy was performed; however, the findings were within normal limits. Initially, the seasonal pattern was not recognized, and the degree of thrombocytopenia was relatively mild; therefore, the patient was followed without intervention. During the current episode, the patient experienced hypothermia severe enough to cause impaired consciousness. At the time of emergency transport, the platelet count was at its lowest recorded level, and the ambient temperature on that day was also significantly low. This prompted us to consider the possibility of seasonal thrombocytopenia related to a thermoregulatory disorder. Because the patient had undergone regular blood sampling, we analyzed the correlation between platelet counts and the average monthly temperature in the patient\u0026rsquo;s prefecture of residence. A clear seasonal trend was observed, with lower platelet counts during the winter months (January\u0026ndash;February) and higher values in the summer (July\u0026ndash;September) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). In addition, a strong positive correlation between temperature and platelet count was identified (Pearson\u0026rsquo;s r\u0026thinsp;=\u0026thinsp;0.819) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB).\u003c/p\u003e \u003cp\u003eThrombocytopenia associated with hypothermia has been classically documented in the context of cardiac bypass surgery performed under hypothermic conditions. Animal studies, such as those conducted in dogs, have demonstrated platelet sequestration in the spleen and liver under hypothermic conditions [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Using radiolabeled platelets, these studies identified the liver\u0026mdash;possibly in combination with the spleen\u0026mdash;as the primary site of platelet sequestration. Notably, the thrombocytopenia observed in these models was reversible upon rewarming. Interestingly, platelet dynamics during hibernation in hamsters also involve temporary storage and subsequent release, likely due to margination along the vessel walls in liver sinusoids [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In the setting of chronic hypothermia, however, additional mechanisms may be involved. In such cases, not only sequestration but also impaired platelet production must be considered [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. There are sporadic reports of pancytopenia attributed to reduced bone marrow activity [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Moreover, platelet function itself may be impaired during hypothermia [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Hypothermia inhibits upregulation of granule membrane protein-140, downregulates the glycoprotein Ib-IX complex, suppresses platelet aggregation, and reduces production of thromboxane B\u003csub\u003e2\u003c/sub\u003e (a stable metabolite of thromboxane A\u003csub\u003e2\u003c/sub\u003e) \u003cem\u003ein vitro\u003c/em\u003e. All of these inhibitory effects are fully reversed upon rewarming the blood to 37\u0026deg;C. Although it remains unclear whether the thrombocytopenia in our patient was primarily due to platelet sequestration, impaired production, or platelet malfunction, he presented with widespread subcutaneous hemorrhages on admission. His platelet count recovered rapidly within a few days of supportive care and rewarming, suggesting a reversible process likely influenced by hypothermia.\u003c/p\u003e \u003cp\u003eIn summary, it is important to recognize that underlying thermoregulatory dysfunction may be present in patients with large PitNETs and unexplained seasonal or periodic thrombocytopenia. Such thermoregulatory dysfunction can occasionally lead to serious complications, including impaired consciousness. Therefore, appropriate precautions regarding temperature management should be taken in collaboration with the patient and their family.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePitNET\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epituitary neuroendocrine tumor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank the co-medical staff at Kyoto University Hospital for their support in the neurocritical care of this patient. We also thank Angela Morben, DVM, ELS, from Edanz (https://jp.edanz.com/ac), for editing a draft of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMT and KS were involved in patient data collection. MT, NS and HI performed the data analysis. YM contributed to the interpretation of results. MT drafted the manuscript, with critical input and revisions from NS, EYH, ST and YM. The manuscript was reviewed for intellectual content by CS and YA. All authors read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no source of funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all patients. This report was approved by the institutional ethics committee (R2088).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of the case report and accompanying images was obtained from the patient and his legal guardians.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMorrison SF, Nakamura K. Central mechanisms for thermoregulation. Annu Rev Physiol. 2019;81:285-308. doi:10.1146/annurev-physiol-020518-114546\u003c/li\u003e\n\u003cli\u003ede Vetten L, Bocca G. Systemic effects of hypothermia due to hypothalamic dysfunction after resection of a craniopharyngioma: case report and review of literature. Neuropediatrics. 2013;44:159-62. doi:10.1055/s-0032-1327773.\u003c/li\u003e\n\u003cli\u003eJapan Meteorological Agency. Monthly climate statistics. https://www.data.jma.go.jp/stats/etrn/view/monthly_s3.php?prec_no=61\u0026amp;block_no=47759. Accessed [20 Apr 2025].\u003c/li\u003e\n\u003cli\u003eNakamura Y, Yahiro T, Fukushima A, Kataoka N, Hioki H, Nakamura K. Prostaglandin EP3 receptor-expressing preoptic neurons bidirectionally control body temperature via tonic GABAergic signaling. Sci Adv. 2022;8:eadd5463. doi:10.1126/sciadv.add5463\u003c/li\u003e\n\u003cli\u003eRatcliffe PJ, Bell JI, Collins KJ, Frackowiak RS, Rudge P. Late onset post-traumatic hypothalamic hypothermia. J Neurol Neurosurg Psychiatry. 1983;46:72-4. doi:10.1136/jnnp.46.1.72\u003c/li\u003e\n\u003cli\u003eMoreira Marques T, Almeida A, Pinheiro J, Nascimento PO. Dysautonomia secondary to third ventriculostomy successfully managed with midodrine. BMJ Case Rep. 2020;13:e232767. doi:10.1136/bcr-2019-232767\u003c/li\u003e\n\u003cli\u003eHidaka T, Ikawa F, Hamasaki O, Kurokawa Y, Yonezawa U, Kurisu K. A case of transient hypothermia after trans-lamina terminalis and third ventricle clipping of an extremely high-position basilar tip aneurysm. SAGE Open Med Case Rep. 2015;3:2050313X15578318. doi:10.1177/2050313X15578318\u003c/li\u003e\n\u003cli\u003eGriffiths AP, Henderson M, Penn ND, Tindall H. Haematological, neurological and psychiatric complications of chronic hypothermia following surgery for craniopharyngioma. Postgrad Med J. 1988;64:617-20. doi:10.1136/pgmj.64.754.617\u003c/li\u003e\n\u003cli\u003eErfurth EM, Holmer H, Fjalldal SB. Mortality and morbidity in adult craniopharyngioma. Pituitary. 2013;16:46-55. doi:10.1007/s11102-012-0428-2\u003c/li\u003e\n\u003cli\u003eGalbiati F, Stamatiades GA, Bi WL, Abreu AP. Hypothalamic and pituitary dysfunction after extensive brain surgery: there is thirst for more knowledge. JCEM Case Rep. 2023;1:luad137. doi:10.1210/jcemcr/luad137\u003c/li\u003e\n\u003cli\u003eHaugh RM, Markesbery WR. Hypothalamic astrocytoma. Syndrome of hyperphagia, obesity, and disturbances of behavior and endocrine and autonomic function. Arch Neurol. 1983;40:560-3. doi:10.1001/archneur.1983.04050080060011\u003c/li\u003e\n\u003cli\u003eJoshi VV, Chaudhuri A, Karnad DR, Tilve GH. Hypothermia due to transient hypothalamic dysfunction in tuberculous meningitis with hydrocephalus. Br J Neurosurg. 1992;6:385-7. doi:10.3109/02688699209023801\u003c/li\u003e\n\u003cli\u003eToledano M, Weinshenker BG, Kaufmann TJ, Parisi JE, Paz Sold\u0026aacute;n MM. Demographics and clinical characteristics of episodic hypothermia in multiple sclerosis. Mult Scler. 2019;25:709-14. doi:10.1177/1352458518767045\u003c/li\u003e\n\u003cli\u003eDevic P, Peter-Derex L, Richard-Mornas A, Ernesto S, Nesme P, Maugui\u0026egrave;re F, et al. Late-onset post-lesional paroxysmal hypothermia: a case series and literature review. J Neurol. 2020;267:3301-9. doi:10.1007/s00415-020-10013-3\u003c/li\u003e\n\u003cli\u003eRossignon P, El Alaoui K, Soupart A. Spontaneous periodic hypothermia with confirmed epilepsy: a report of two cases. Eur J Case Rep Intern Med. 2023;10:003960. doi:10.12890/2023_003960\u003c/li\u003e\n\u003cli\u003eMorgan M, Schwartz L, Duflou J. Hypothermia secondary to glioblastoma multiforme? Autopsy findings in two cases. J Forensic Sci. 2015;60:511-3. doi:10.1111/1556-4029.12699\u003c/li\u003e\n\u003cli\u003eWard ME, Cowley AR. Hypothermia: a natural cause of death. Am J Forensic Med Pathol. 1999;20:383-6. doi:10.1097/00000433-199912000-00014\u003c/li\u003e\n\u003cli\u003eSuzuki H, Hayashi K, Fukunaga T. Two forensic autopsy cases of death from unexpected lesions of the pituitary gland. Leg Med (Tokyo). 2014;16:36-9. doi:10.1016/j.legalmed.2013.10.004\u003c/li\u003e\n\u003cli\u003eErlich-Malona N, Bartolini L, D\u0026apos;Abreu A, Roth J. Paroxysmal hypothermia with prominent parkinsonian features after suprachiasmatic tumor resection. Neurohospitalist. 2022;12:285-9. doi:10.1177/19418744211056206\u003c/li\u003e\n\u003cli\u003eVillalobos TJ, Adelson E, Riley PA Jr, Crosby WH. A cause of the thrombocytopenia and leukopenia that occur in dogs during deep hypothermia. J Clin Invest. 1958;37:1-7. doi:10.1172/JCI103576\u003c/li\u003e\n\u003cli\u003eHessel EA 2nd, Schmer G, Dillard DH. Platelet kinetics during deep hypothermia. J Surg Res. 1980;28:23-34. doi:10.1016/0022-4804(80)90078-5\u003c/li\u003e\n\u003cli\u003ede Vrij EL, Bouma HR, Goris M, Weerman U, de Groot AP, Kuipers J, et al. Reversible thrombocytopenia during hibernation originates from storage and release of platelets in liver sinusoids. J Comp Physiol B. 2021;191:603-15. doi:10.1007/s00360-021-01351-3\u003c/li\u003e\n\u003cli\u003eO\u0026apos;Brien H, Amess JA, Mollin DL. Recurrent thrombocytopenia, erythroid hypoplasia and sideroblastic anaemia associated with hypothermia. Br J Haematol. 1982;51:451-6.\u003c/li\u003e\n\u003cli\u003eMichelson AD, MacGregor H, Barnard MR, Kestin AS, Rohrer MJ, Valeri CR. Reversible inhibition of human platelet activation by hypothermia in vivo and in vitro. Thromb Haemost. 1994;71:633-40.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"hypothermia, hypothalamus, thrombocytopenia, pituitary neuroendocrine tumor, case report","lastPublishedDoi":"10.21203/rs.3.rs-6591159/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6591159/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe hypothalamus plays a central role in thermoregulation. In brain tumors involving the hypothalamus, hypothermia can lead to rare but serious complications such as impaired consciousness and thrombocytopenia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase Presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAn 80-year-old man was brought to our hospital in February after being found unresponsive in his bedroom. He had a history of surgery for a giant PitNET at another institution and was subsequently followed at our hospital. Having declined further surgical intervention, he was managed conservatively. During follow-up, episodes of unexplained paroxysmal thrombocytopenia were occasionally observed. Upon arrival, he was comatose with a core body temperature of 32.1°C. Laboratory tests revealed marked thrombocytopenia (55,000/µL) and widespread subcutaneous hemorrhages. Hypothermia was considered the primary cause of the impaired consciousness. Because the patient’s body temperature was gradually normalized by external warming, his level of consciousness improved, and his platelet count also began to recover over the following days. A retrospective review of prior laboratory data revealed a seasonal pattern in the thrombocytopenia. Based on these findings, the thrombocytopenia was considered secondary to hypothalamic hypothermia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHypothalamic tumors can precipitate hypothermia and seasonal hematologic disturbances. In patients with brain tumors presenting with unexplained, seasonal, or periodic thrombocytopenia, underlying thermoregulatory dysfunction due to hypothalamic involvement should be considered.\u003c/p\u003e","manuscriptTitle":"Seasonal Thrombocytopenia Induced by Hypothalamic Hypothermia: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-18 06:35:47","doi":"10.21203/rs.3.rs-6591159/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-06-17T06:29:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"32806379570479685975657294962364436221","date":"2025-06-15T13:27:32+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-13T17:23:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"321328252553780035979090225876914916770","date":"2025-06-13T16:41:52+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-13T12:44:55+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-11T11:20:03+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-05-21T22:30:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-20T13:24:28+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2025-05-20T13:23:23+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7397560a-c611-46a0-9296-f03558e49505","owner":[],"postedDate":"June 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-06-18T06:35:47+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-18 06:35:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6591159","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6591159","identity":"rs-6591159","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}