CME INDIA Case Presentation by Dr. Ashish Gautam, Prof. of Medicine, P. G. Department of Medicine, S.N. Medical College, Agra, India.
CME INDIA Case Study
How Presented?
- One 42 yrs. female, otherwise healthy and totally unaware of the fact that she started developing forgetfulness from the last 2-3 months.
- All previous memories were intact but registration for the new event was almost 90% lost.
- Forgets all events such as what she had in dinner last night? Where she has kept the keys? And any matter discussed by husband a day before.
- She also developed too much fatigue and loss of appetite.
- Preferred to sleep most of the time.
- She also developed burning and pain in the oral cavity from the last two months which is identified by the dental surgeon as probable histiocytosis (See biopsy report).
- No headache, no problem in any sensory, motor function, cerebellar or autonomic function.
- All cranial nerves are intact.
- Field of vision and fundus examination will be done in due course.
- CBC TSH LFT RFT RBG all normal.
- Cortisol level fasting 8 AM was 1.3 mcg/dl, S ACE levels was 25.8 U/L, Estradiol level (E2) <11.8 pg/ml, ANA 52.4 Units, S Prolactin level 113.2 ng/ml, HbsAg, Anti HCV, HIV 1 & 2 Negative.
- Blood pressure in supine position was 100/60 mmHg and 70/60 mmHg in sitting posture.
Important Investigations
NCCT Thorax showing an old tubercular scar (which happened 20 years back).
MRI contrast is being posted
CME INDIA Discussion
Dr. Anil Kumar, Consultant psychiatrist, Ranchi:
- Looks like pseudo dementia. Give her antidepressants.
Dr. Basab Ghosh, Agartala:
- I thought, we should think in the line of dementia.
- Low dose Donepezil could try.
Dr. Ashish Gautam, Prof of Medicine, Agra:
- But oedema in hypothalamus and surrounding is matter of concern which could be possible reason for clinical the manifestation.
Dr. Anil Kumar, Consultant psychiatrist, Ranchi:
- Yes. Agree.
- Hypothalamus lesions can manifest as pseudodementia.
- Neurosurgeon opinion.
- Endocrinologist opinion.
Dr. Raju Sharma, Sr. Physician, Jamshedpur:
- Rule out prion.
- I know that a frightening thing to think of, also B12 deficiency.
Dr. Anil Kumar, Consultant psychiatrist, Ranchi:
- No
Dr. Amit Agarwal, DM Neuro, Jamshedpur, AIIMS:
- In my opinion she will require MR Spectroscopy of the lesion and to rule out demyelinating versus SOL which can be done by brain biopsy.
Dr. Ashok Kumar, DM Neuro, Ranchi:
- Intensely enhancing Suprasellar mass – Isointense to Grey matter in T1. Pressing on 3rd ventricle floor. There is oedema in this floor (Hypothalamus) and Inferomedial Thalamus.
- Looks like GERMINOMA.
- Sleep and Weight loss is Hypothalamic. Memory problems due to Papez circuit involvement (anatomy is slightly anterior).
- Get MRS.
- Blood and CSF – hCG.
Dr. Namrata Chauhan, DM, Neurology, Associate Professor NSCB, Jabalpur:
- MRI is suggestive of LCH.
- Possibly, Langerhans cell histiocytosis.
- Biopsy report please share if it’s done.
- Granular cell tumour.
- I had D/D of LCH / sarcoidosis in mind, radiologist added granular cell tumour to the list.
- If it’s LCH, radio / immunotherapy (any good centre with this facility) and chemotherapy at a good oncological centre with good radio / chemo protocols needed.
What happened Next?
Ophthalmological Examination
As per ophthalmologist slight non specific changes on left upper quadrants B/L.
- It’s LCH on histopathology.
- Immunohistochemistry is just for further clarification.
Biopsy:
PET Scan:
Biopsy with Immunochemistry
Diagnosis
Hypothalamo-Pituitary Abnormalities with Langerhans Cell Histiocytosis.
CME INDIA Learning Edge
- Langerhans Cell Histiocytosis (LCH) is an uncommon condition, primarily affecting children, and displaying a wide range of clinical presentations.
- Langerhans Cell Histiocytosis (LCH) is a rare disorder characterized by the proliferation of clonal dendritic cells, and it has the potential to impact any organ within the bod.
- In adults, LCH accounts for less than 30% of all reported cases, with an estimated incidence of approximately 1.8 per one million individuals. However, the full extent and long-term outcomes of LCH in adults remain inadequately defined.
- Notably, anterior pituitary dysfunction has been observed in as many as 20% of LCH patients, often in conjunction with Diabetes Insipidus.
- Such dysfunction has also been noted following radiation therapy.
- Currently, there are no globally recognized and universally accepted international guidelines specifically tailored for the diagnosis and treatment of adult patients with Langerhans Cell Histiocytosis (LCH). This underscores the rarity and complexity of the condition, which often leads to variability in clinical approaches and management strategies.
- Langerhans Cell Histiocytosis (LCH) is a condition known for its potential to affect various organs or systems in the body. Among these, the most commonly affected areas include bones, skin, and the pituitary gland. However, LCH can also manifest in other locations, albeit less frequently. These fewer common sites of involvement may include lymph nodes, liver, spleen, gastrointestinal tract, the central nervous system, and the hematopoietic system.
- Interestingly, pulmonary involvement is another facet of LCH. While it can occur simultaneously with other organ involvement or develop subsequently, isolated pulmonary LCH (PLCH) is relatively common in adult patients. PLCH refers to LCH that primarily affects the lungs. It’s worth noting that in some cases, pulmonary LCH can progress to involve multiple organ systems, leading to a more widespread or multisystem presentation of the disease.
- Diagnosis: The diagnosis of Langerhans Cell Histiocytosis (LCH) is typically established through histologic and immunophenotypic examination of a tissue biopsy taken from the affected lesion. In particular, pathologists and clinicians often look for the presence of Langerhans cells, which are a type of immune cell implicated in the condition.
- One common immunohistochemical marker used to identify Langerhans cells is CD1a. Langerhans cells typically stain positively for CD1a, and this marker is frequently employed in the diagnostic process. Another marker that may be used is Langerin, also known as CD207. A positive stain for CD1a and/or Langerin can support the diagnosis of LCH.
- These immunophenotypic markers, along with the histological features of the biopsy, are essential for distinguishing LCH from other conditions and confirming the diagnosis. An accurate diagnosis is crucial for determining the appropriate course of treatment and management for LCH patients.
- Langerhans Cell Histiocytosis (LCH) often shows a preference for affecting the hypothalamo-pituitary (HP) region of the brain. This involvement can lead to permanent hormonal deficiencies in both the posterior and/or anterior pituitary glands in some individuals.
- One of the most common consequences related to LCH in this region is Diabetes Insipidus (DI). DI can either precede the formal diagnosis of LCH or develop at any point during the progression of the disease. DI is characterized by excessive thirst and urination due to the inability of the kidneys to concentrate urine properly, which results from insufficient production or action of antidiuretic hormone (ADH), also known as vasopressin. Managing DI and other hormonal deficiencies in LCH patients is an important aspect of their medical care and often requires ongoing treatment and monitoring.
- Anterior pituitary dysfunction (APD) is a significant issue in patients with Langerhans Cell Histiocytosis (LCH). Studies have shown that up to 20% of LCH patients may experience anterior pituitary dysfunction, and this dysfunction is often accompanied by Diabetes Insipidus (DI). This combination of anterior pituitary hormonal deficiencies and DI can result from the involvement of LCH in the hypothalamo-pituitary (HP) region of the brain. It underscores the importance of closely monitoring and managing hormone imbalances in LCH patients, as these deficiencies can have a significant impact on their overall health and well-being.
- This case is a very rare. Hypothalamic involvement in Langerhans Cell Histiocytosis (LCH) is less common than pituitary involvement, but when it does occur, it can have a wide range of effects beyond just pituitary dysfunction. Hypothalamic involvement can lead to a spectrum of issues, including:
- Neuropsychiatric and Behavioral Disorders: LCH-related damage to the hypothalamus can result in neuropsychiatric symptoms and behavioral disturbances. These may include mood swings, cognitive changes, and altered emotional states.
- Disturbances of Thermo-regulation: The hypothalamus plays a crucial role in regulating body temperature. Damage to this area can lead to difficulties in temperature regulation, potentially causing issues like hyperthermia or hypothermia.
- Sleeping Pattern Disturbances: The hypothalamus is involved in regulating the sleep-wake cycle. Hypothalamic involvement can disrupt normal sleeping patterns, leading to sleep disturbances or insomnia.
- Autonomic Abnormalities: The autonomic nervous system, responsible for controlling involuntary bodily functions, is influenced by the hypothalamus. Damage to this area can result in autonomic abnormalities, potentially affecting functions like heart rate, blood pressure, and digestion.
- Metabolic Abnormalities: The hypothalamus is also involved in regulating metabolic processes, including hunger and thirst. Disruption of hypothalamic function can lead to metabolic abnormalities, potentially causing issues with appetite and hydration.
- These diverse effects highlight the complex and multifaceted nature of LCH when it involves the hypothalamus. The management of such cases often requires a multidisciplinary approach involving endocrinologists, neurologists, and psychiatrists, among other specialists, to address the various aspects of the condition and its impact on the patient’s overall health and quality of life.
- There was no universally accepted standard therapeutic approach specifically tailored for adult patients with Langerhans Cell Histiocytosis (LCH). The management of LCH in adults is indeed highly individualized and depends on several factors.
- This case appears to be rare having Isolated hypothalamic-pituitary langerhans’ cell histiocytosis in a female adult.
Further Readings:
- Girschikofsky M, Arico M, Castillo D, Chu A, Doberauer C, Fichter J, Haroche J, Kaltsas GA, Makras P, Marzano AV, de Menthon M, Micke O, Passoni E, Seegenschmiedt HM, Tazi A, McClain KL. Management of adult patients with Langerhans cell histiocytosis: recommendations from an expert panel on behalf of Euro-Histio-Net. Orphanet J Rare Dis. 2013 May 14;8:72. doi: 10.1186/1750-1172-8-72. PMID: 23672541; PMCID: PMC3667012.
- Kurtulmus N, Mert M, Tanakol R, Yarman S. The pituitary gland in patients with Langerhans cell histiocytosis: a clinical and radiological evaluation. Endocrine. 2015 Apr;48(3):949-56. doi: 10.1007/s12020-014-0408-6. Epub 2014 Sep 11. PMID: 25209890.
- Kaltsas GA, Powles TB, Evanson J, Plowman PN, Drinkwater JE, Jenkins PJ, Monson JP, Besser GM, Grossman AB. Hypothalamo-pituitary abnormalities in adult patients with langerhans cell histiocytosis: clinical, endocrinological, and radiological features and response to treatment. J Clin Endocrinol Metab. 2000 Apr;85(4):1370-6. doi: 10.1210/jcem.85.4.6501. PMID: 10770168.
- Tan H, Yu K, Yu Y, An Z, Li J. Isolated hypothalamic-pituitary langerhans’ cell histiocytosis in female adult: A case report. Medicine (Baltimore). 2019 Jan;98(2):e13853. doi: 10.1097/MD.0000000000013853. PMID: 30633157; PMCID: PMC6336579.
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