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Incomplete Deficiency of Hypothalamic Hormones in Hypothalamic Hypopituitarism Associated with an Old Traumatic Brain Injury
Open accessAbstract
A 62 year-old man was admitted to determine the pathogenesis of his hypoglycemia. He was unconscious and his plasma glucose level was 26 mg/dL. When he was 31 years old, he had a traffic accident and was unconscious for several days. Physical findings on admittance showed that the patient's BMI was 17.8 and blood pressure, 114/70 mmHg. He was alert. He had a hypogonadal face with a lack of beard, and he had an atrophic testis with a volume of 1 to 2 ml. Laboratory findings showed that his fasting plasma glucose was 73 mg/dL; serum sodium, 133 mmol/l; potassium, 4.1 mmol/l; serum insulin, less than 1.0 muU/ml.; plasma ACTH, 45.8 pg/ml; serum cortisol, 5.2 microg/dL; and free cortisol urinary excretion, less than 4.5 microg/day; serum LH, 0.8 mIU/ml; serum testosterone, less than 0.05 ng/ml; serum TSH, 2.0 uIU/ml; free T(4), 0.7 ng/dL; free T(3), 1.5 pg/ml; and serum prolactin, 29.0 ng/ml. The levels of all the pituitary hormones were elevated in response to a mixture of exogenous corticotrophin-releasing hormone (CRH), luteinizing hormone-releasing hormone (LH-RH), thyrotropin-releasing hormone (TRH), and growth hormone-releasing hormone (GRH). However, there was no increased secretion of adrenocorticotropic hormone (ACTH) in response to hypoglycemia (induced by the administration of insulin) and there was no increased secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH) in response to the administration of clomiphene. Magnetic resonance imaging revealed an atrophied pituitary gland with an empty sella, but there were no abnormal findings of the hypothalamus. Hydrocortisone replacement at a dosage of 20 mg/day increased the patient's plasma glucose from 73 to 100 mg/dL and his serum sodium from 133 to 138 mmol/l. These findings therefore indicate a partial impairment in hypothalamic hormone release, resulting from a traumatic brain injury that the patient had received 31 years ago.
Overview
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TL;DR
This case report describes a 62-year-old man with severe hypoglycemia and hypopituitarism attributed to a traumatic brain injury 31 years earlier. Endocrine testing indicated partial hypothalamic hormone deficiency: the anterior pituitary responded to exogenous hypothalamic hormones but not to central stimuli, and MRI showed an atrophic pituitary with empty sella but no hypothalamic lesion.
Key findings
- Hypoglycemia was the presenting feature: initial plasma glucose was 26 mg/dL, and later fasting plasma glucose was 73 mg/dL with insulin <1.0 µU/mL; hydrocortisone 20 mg/day increased plasma glucose from 73 to 100 mg/dL and serum sodium from 133 to 138 mmol/L.
- Basal testing showed central hypogonadism, hypocortisolism, and low thyroid hormone levels: LH 0.8 mIU/mL, testosterone <0.05 ng/mL, cortisol 5.2 µg/dL, urinary free cortisol <4.5 µg/day, free T4 0.7 ng/dL, and free T3 1.5 pg/mL.
- Pituitary hormones rose after exogenous CRH, LH-RH, TRH, and GRH (e.g., ACTH >300 pg/mL at 30 min after CRH; TSH, GH, and prolactin rose after TRH/GRH; LH and FSH rose after LH-RH), but there was no ACTH or GH response to insulin-induced hypoglycemia and no LH/FSH response to clomiphene.
- MRI revealed an atrophied pituitary gland with an empty sella and no abnormal hypothalamic findings; the authors concluded that incomplete/partial hypothalamic hormone release impairment had persisted approximately 31 years after traumatic brain injury.
Methods
- Single case report of a 62-year-old man admitted to evaluate severe hypoglycemia; he had a history of traumatic brain injury at age 31 with loss of consciousness for several days and had lost pubic and axillary hair several months after the accident.
- Endocrine evaluation included basal pituitary, adrenal, gonadal, and thyroid axis measurements; combined stimulation with CRH, LH-RH, TRH, and GRH; insulin-induced hypoglycemia; clomiphene testing; ACTH challenge; and brain MRI.
- The main analysis was descriptive, reporting hormone responses and the clinical course after hydrocortisone 20 mg/day and later thyroxine 50 µg/day.
Limitations
- Stated: the details of the patient’s brain injury are unclear.
- Evident from the design: as a single case report, the findings cannot establish causality, prevalence, or generalizability; there was no control or comparison group and no histopathologic confirmation, and localization to a restricted hypothalamic region is inferred because MRI showed no hypothalamic abnormality.
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Claims the paper makes
0 Valid · 0 Not valid · 7 Not checked · 28 Own results and interpretations
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“there was no increased secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSh) in response to the administration of clomiphene.”
- Also stated in: § Case Report · plain
“by contrast, there was no Lh and FSh release in response to the oral administration of clomiphene (Fig. 1d).”
§ Incomplete Deficiency of Hypothalamic Hormones in Hypothalamic Hypopituitarism Associated with an Old Traumatic Brain Injury > Abstract
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Case Report · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“free T 4 , 0.7 ng/dL”
- Also stated in: § Case Report · plain
“serum free T 4 , 0.7 ng/dL”
§ Incomplete Deficiency of Hypothalamic Hormones in Hypothalamic Hypopituitarism Associated with an Old Traumatic Brain Injury > Abstract
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Case Report · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and his serum sodium from 133 to 138 mmol/L.”
- Also stated in: § Clinical course · plain
“his serum Na level increased to 138 mmol/L.”
§ Incomplete Deficiency of Hypothalamic Hormones in Hypothalamic Hypopituitarism Associated with an Old Traumatic Brain Injury > Abstract
plainstates a causeSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Clinical course · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“plasma ACTH, 45.8 pg/mL”
- Also stated in: § Case Report · plain
“plasma ACTH level was 45.8 pg/mL”
§ Incomplete Deficiency of Hypothalamic Hormones in Hypothalamic Hypopituitarism Associated with an Old Traumatic Brain Injury > Abstract
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Case Report · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Several months after the accident, he had lost pubic and axillar hair.”
- Also stated in: § Discussion · plain
“He had lost his pubic and axillar hair several months after the traumatic brain injury.”
§ Incomplete Deficiency of Hypothalamic Hormones in Hypothalamic Hypopituitarism Associated with an Old Traumatic Brain Injury > Case Report
plainstates an associationSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Discussion · plain
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Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Incomplete Deficiency of Hypothalamic Hormones in Hypothalamic Hypopituitarism Associated with an Old Traumatic Brain Injury > Clinical course
“As noted above, there were no abnormal findings on the MRI.”
§ Incomplete Deficiency of Hypothalamic Hormones in Hypothalamic Hypopituitarism Associated with an Old Traumatic Brain Injury > Case Report
“Brain magnetic resonance imaging (MRI) showed an atrophied pituitary gland with an empty sella.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Incomplete Deficiency of Hypothalamic Hormones in Hypothalamic Hypopituitarism Associated with an Old Traumatic Brain Injury > Case Report
“The LH-RH challenge test indicated delayed, but significant increases in serum Lh and FSh levels (Fig. 1c).”
§ Incomplete Deficiency of Hypothalamic Hormones in Hypothalamic Hypopituitarism Associated with an Old Traumatic Brain Injury > Clinical course
“As noted earlier, challenge tests (i.e., the administration of exogenous hypothalamic hormones) promptly increased the release of ACTH, TSH, GH, and gonadotropin.”
Citations
Cites
The epidemiology of traumatic brain injury: a review
Bruns, J., & Hauser, W. A. (2003) · Epilepsia · doi:10.1046/j.1528-1157.44.s10.3.x · Cited by 1,271
The Diagnosis of Head Injury Requires a Classification Based on Computed Axial Tomography
Marshall, L. F., Marshall, S. B., Klauber, M. R., van Berkum-Clark, M., Eisenberg, H., Jane, J. A., Luerssen, T. G., Marmarou, A., & Foulkes, M. A. (1992) · Journal of Neurotrauma · doi:10.1177/089771519200901s26 · Cited by 814
Kelly, D. F., Gaw Gonzalo, I. T., Cohan, P., Berman, N., Swerdloff, R., & Wang, C. (2000) · Journal of Neurosurgery · doi:10.3171/jns.2000.93.5.0743 · Cited by 455
Hypopituitarism Secondary to Head Trauma
Benvenga, S. (2000) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.4.1353 · Cited by 423
Residual pituitary function after brain injury-induced hypopituitarism: a prospective 12-month study
Aimaretti, G., Ambrosio, M. R., Di Somma, C., Gasperi, M., Cannavò, S., Scaroni, C., Fusco, A., Del Monte, P., De Menis, E., Faustini-Fustini, M., et al. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0504 · Cited by 370
Aimaretti, G., Ambrosio, M. R., Di Somma, C., Fusco, A., Cannavò, S., Gasperi, M., Scaroni, C., De Marinis, L., Benvenga, S., Uberti, E. C. D., et al. (2004) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2004.02094.x · Cited by 339
Occurrence of pituitary dysfunction following traumatic brain injury
Bondanelli, M., De Marinis, L., Ambrosio, M. R., Monesi, M., Valle, D., Zatelli, M. C., Fusco, A., Bianchi, A., Farneti, M., & Degli, E. C. I. (2004) · Journal of Neurotrauma · doi:10.1089/0897715041269713 · Cited by 322
Neuroendocrine dysfunction in the acute phase of traumatic brain injury
Agha, A., Rogers, B., Mylotte, D., Taleb, F., Tormey, W., Phillips, J., & Thompson, C. J. (2004) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2004.02023.x · Cited by 313
Prevalence of Neuroendocrine Dysfunction in Patients Recovering from Traumatic Brain Injury
Lieberman, S. A. (2001) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.86.6.2752 · Cited by 261
1. Brain injury: Epidemiology and pathophysiology
Greenwald, B. D., Burnett, D. M., & Miller, M. A. (2003) · Archives of Physical Medicine and Rehabilitation · doi:10.1053/apmr.2003.50052 · Cited by 180
Cited by
Differences according to Sex in Sociosexuality and Infidelity after Traumatic Brain Injury
Moreno, A., & McKerral, M. (2015) · Behavioural Neurology · doi:10.1155/2015/914134 · Cited by 8
A case of hypothalamic hypopituitarism accompanied by recurrent severe hypoglycemia
Takai, M., Kaneto, H., Kamei, S., Mune, T., & Kaku, K. (2015) · SpringerPlus · doi:10.1186/s40064-015-0934-6 · Cited by 8
Kageyama, K., Sato, K., Yamagata, S., Tasso, M., Nakada, Y., & Sawada, S. (2026) · Clinical Case Reports · doi:10.1002/ccr3.73582
(2012) · Elsevier eBooks · doi:10.1016/b978-3-437-41797-9.16001-7
Metadata
- Authors
- SAITO, T., SATO, N., KIMOTO, M., ASANO, T., AOKI, A., IKOMA, A., TOYOSHIMA, H., KAWAKAMI, M., & ISHIKAWA, S.-E.
- Affiliations
- Jichi Medical University Saitama Medical Center (JP)
- Department of Medicine, Jichi Medical University Saitama Medical Center, Saitama , Japan
- Venue
- Endocrine Journal
- Publisher
- Japan Endocrine Society
- Published
- 2009
- Volume
- 56
- Issue
- 8
- Pages
- 945-950
- ISSN
- 0918-8959 (ISSN-L)
- 1348-4540
- OpenAlex
- W1976788284
- Semantic Scholar
- 08ba50685e1ca90d1167f4045e8180c43474a6c4
- Cited by
- 4
- References
- 11
- Citations by year
- 2026: 1 · 2015: 2 · 2012: 1
- FWCI
- 0.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrine Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- traumatic brain injury, hypoglycemia, hypopituitarism, ACTH deficiency, hydrocortisone replacement, pituitary atrophy, empty sella, hypogonadism, growth hormone deficiency, prolactin, insulin-induced hypoglycemia
- MeSH terms
- Brain Injuries, Diagnosis, Differential, Diagnostic Techniques, Endocrine, Humans, Hypopituitarism, Hypothalamic Hormones, Male, Middle Aged, Time Factors
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