Alterations of the GH/IGF-I Axis and Gut Microbiome after Traumatic Brain Injury: A New Clinical Syndrome?

CONTEXT: Pituitary dysfunction with abnormal growth hormone (GH) secretion and neurocognitive deficits are common consequences of traumatic brain injury (TBI). Recognizing the comorbidity of these symptoms is of clinical importance; however, efficacious treatment is currently lacking. EVIDENCE ACQUISITION: A review of studies in PubMed published between January 1980 to March 2020 and ongoing clinical trials was conducted using the search terms "growth hormone," "traumatic brain injury," and "gut microbiome." EVIDENCE SYNTHESIS: Increasing evidence has implicated the effects of TBI in promoting an interplay of ischemia, cytotoxicity, and inflammation that renders a subset of patients to develop postinjury hypopituitarism, severe fatigue, and impaired cognition and behavioral processes. Recent data have suggested an association between abnormal GH secretion and altered gut microbiome in TBI patients, thus prompting the description of a hypothesized new clinical syndrome called "brain injury associated fatigue and altered cognition." Notably, these patients demonstrate distinct characteristics from those with GH deficiency from other non-TBI causes in that their symptom complex improves significantly with recombinant human GH treatment, but does not reverse the underlying mechanistic cause as symptoms typically recur upon treatment cessation. CONCLUSION: The reviewed data describe the importance of alterations of the GH/insulin-like growth factor I axis and gut microbiome after brain injury and its influence in promoting neurocognitive and behavioral deficits in a bidirectional relationship, and highlight a new clinical syndrome that may exist in a subset of TBI patients in whom recombinant human GH therapy could significantly improve symptomatology. More studies are needed to further characterize this clinical syndrome.

Pituitary tuberculosis presented with pituitary coma.

BACKGROUND: Pituitary tuberculosis is very rare. Its diagnosis is difficult unless a bacteriological or histological evidence of tuberculosis. OBSERVATION: We report the case of a 54 years old woman who presented with a pituitary coma that occurred two weeks after the initiation of antituberculous therapy for cervical lymph node tuberculosis. Resonance magnetic imaging showed a pseudotumoral aspect of the pituitary gland. She had hormonal replacement and anti-tuberculous therapy. Outcome was favourable with the normalization of both the pituitary function and the pituitary volume. However, an acute hypopituitarism happened eight months after the withdrawal of antituberculous, which were taken during 12 months. The re initiation of anti tuberculous therapy and its extension to two years leaded to a prolonged remission. CONCLUSION: the three-phase outcome confirms the tuberculous origin of the hypophysitis in our patient.

Hypopituitarism as consequence of late neonatal infection by Group B streptococcus: a case report.

Hypopituitarism is a condition characterized by dysfunction of the pituitary gland hormone production. The insults of the perinatal period, which includes the late infection by Group B Streptococcus, consists in a rare etiology of this condition. We present the case of a 39-days-old infant with meningitis caused by Streptococcus Group B, which showed, among other consequences, hypopituitarism.

The importance of not jumping to conclusions: syphilis as an organic cause of neurological, psychiatric and endocrine presentations.

A 66-year-old Caucasian man was admitted to an acute psychiatric ward under section 2 of the Mental Health Act after presenting with auditory hallucinations and partition delusions. He had been known to mental health services since 2005 but had never been treated with psychotropic medication or given a formal psychiatric diagnosis. He was also diagnosed with hypopituitarism of unknown aetiology in 2002. In light of this presentation, his medical history was reviewed in full, hormone levels and a full delirium screen including blood borne virus and syphilis serology was completed to ensure no organic cause had been missed. The treponemal antibody was positive, and he reported no previous syphilis treatment, as such a diagnosis of neurosyphilis was performed. This case demonstrates a patient presenting with two potential complications of syphilis; psychosis and hypopituitarism where screening for this infection had not been previously considered.

Acute hypophysitis and hypopituitarism in early syphilitic meningitis in a HIV-infected patient: a case report.

BACKGROUND: Sexually transmitted diseases and most notably syphilis-infections are rising amongst men who have sex with men. In HIV-co-infected patients, an accelerated clinical course of syphilis neurological involvement is known. CASE PRESENTATION: A 46 year old HIV-positive male patient came in to our emergency department in the late evening with acute fever, rapidly progressive cephalgia and photophobia. Palmar skin efflorescence was evocative of an active syphilis infection. A reactive Treponema pallidum particle agglutination (TPPA) assay with positive Treponema pallidum-specific IgG/IgM immunofluorescence as well as a highly reactive Veneral diseases research laboratory (VDRL) test confirmed the diagnosis. Liquor pleocytosis, liquor protein elevation and a highly positive VDRL test in cerebrospinal fluid (CSF) were interpreted in context of the clinical symptoms as neurosyphilitic manifestations within an early syphilis infection (stage II). Cranial nuclear magnetic resonance scans of the sella turcica, which were performed due to low thyroidea stimulation hormone (TSH) and thyroxin levels, showed signs of hypophysitis such as pituitary gland enlargement and inhomogeneous contrast enhancement. Advanced endocrine laboratory testing revealed hypopituitarism. Fourteen days of intravenous ceftriaxone treatment and levothyroxine- and hydrocortisone-substitution led to complete disappearance of all clinical symptoms. Two months later, nuclear magnetic resonance scan showed normal pituitary size and that the syphilis serology had normalized. CONCLUSION: We report to the best of our knowledge the first case of a HIV-positive patient with acute hypophysitis and hypopituarism due to early neurosyphilis infection. Ceftriaxone treatment and levothyroxine- and hydrocortisone-substitution led to the disappearance of all clinical symptoms. We strongly recommend to exclude syphilis infection in every clinical situation unclear in HIV-patients, especially when additional risk factors are known.

Blastomycosis of the central nervous system in a child: a rare cause of hypopituitarism.

Blastomyces dermatitidis is a dimorphic fungus that can cause granulomatous lesions. Typically, children present with respiratory symptoms. Central nervous system involvement is unusual, and almost always associated with involvement of other organs. This case report, to our knowledge, is the first published case of an adolescent male presenting with panhypopituitarism secondary to a blastomycosis infection.

Pituitary abscess.

Pituitary abscess is a rare disease, but one with potentially high mortality and morbidity. We present a 46-year-old man with progressive visual disturbance and general malaise for 1 year. Endocrine studies revealed hypopituitarism, and magnetic resonance imaging revealed a pituitary lesion with suprasellar extension. We attempted to excise the lesion using a transsphenoidal approach, but pus in the pituitary fossa was found at operation, and no tumour was identified. The culture yielded coagulase-negative Staphylococcus. Antibiotics were administered for 3 weeks, and the patient made a good postoperative recovery. He required life-long hormone replacement therapy. After one and a half years of follow-up, he was well and had no evidence of focal or systemic infection. We review the literature regarding pituitary abscess and discuss the appropriate treatment and possible pathological mechanism.

Childhood panhypopituitarism presenting as child abuse: a case report and review of the literature.

Childhood panhypopituitarism may be acquired or congenital. Children with panhypopituitarism can present clinically with diabetes, growth failure, decreased bone density, and morbid obesity. In the forensic setting without the proper history, it can be misdiagnosed as child abuse or neglect. We report a case of a 3-year-old black girl who was admitted to the emergency room with apnea and subsequently died. While at the emergency department, it was discovered that the child had a fractured left hip and was severely growth retarded for age. The coroner wanted to rule out child abuse and/or neglect and requested an autopsy based on the physical findings identified by hospital staff. Significant findings at autopsy included small for age (15th percentile for age), hypoplastic brain/pituitary gland/adrenal gland/thyroid gland, abnormally formed skull with an occipital protuberance, a fractured left hip with decreased bone density, and central adiposity. Subsequent to the autopsy, it was discovered that at 6 weeks of age the child suffered from group B streptococci meningitis that resulted in panhypopituitarism. The panhypopituitarism then resulted in seizure activity, diabetes insipidus, and growth retardation. The authors hope this case report and review of the literature will assist investigators, pathologists, and clinicians in making a distinction between neglect or inflicted injury of child abuse and panhypopituitarism that can present with similar signs and symptoms.

Bacterial pituitary abscess: an unusual cause of panhypopituitarism.

OBJECTIVE: To describe a case of primary bacterial pituitary abscess manifesting as hypopituitarism. METHODS: We present the case history, hormonal and bacteriologic data, and findings on imaging studies in a 34-year-old man. RESULTS: The patient had an 8-month history of intermittent fever, headache, nausea, vomiting, and weight loss. Because a computed tomographic scan of the head showed a cystic sellar mass with ring enhancement, he was referred to our medical center. On physical examination, he showed signs of meningeal irritation and had mild hypotension. Hormonal evaluation revealed evidence of hypocortisolism, hypothyroidism, and hypogonadism. Three weeks after treatment with antibiotics and hormonal replacement, he underwent transsphenoidal surgical exploration and evacuation of purulent material from the sella. On culture, this specimen grew coagulase-negative staphylococci and Propionibacterium granulosum. Nine months later, dynamic testing showed persistent central hypocortisolism, hypothyroidism, and hypogonadism. CONCLUSION: Bacterial pituitary abscess is rare but manifests similar to other pituitary masses with headaches, visual field defects, and hormonal disturbances. For the correct preoperative diagnosis of this condition, the physician must have a high index of suspicion, and the characteristic ring enhancement must be present on imaging studies.

Relapsing Whipple's disease presenting with hypopituitarism.

A 44-year-old man with a history of Whipple's disease 8 years ago presented with recurrent grand mal seizures and signs of hypopituitarism on physical examination. Magnetic resonance imaging of the brain revealed a hypothalamic lesion of 1 cm diameter in the region of the rostral infundibulum. Hypopituitarism was confirmed by low levels of serum cortisol, free testosterone and free thyroxine without an elevated TSH. Whipple encephalitis with hypothalamic involvement was suggested and verified by positive polymerase chain reaction (PCR) for Tropheryma whippelii in the cerebrospinal fluid. PCR for T. whippelii has become an important diagnostic tool for establishing the diagnosis of Whipple's disease especially in patients with unusual presentations and if the diagnosis cannot be confirmed histologically. Whipple's disease should be included in the differential diagnosis in hypopituitarism caused by infectious disease.