Pituitary Hormone Involvement in Tuberculous Meningitis

protein was raised, sugar was low. 38 TBM cases had suggestive neuroimaging, where basal exudates and gyral enhancement were the most common radiological abnormality noticed. More than one hormone disbalance was noted in 9 cases. Serum cortisol and ACTH was low in 20% cases, while serum prolactin was high in 7.5% cases. SIADH was diagnosed in 15% cases. Testosterone was low in 3.7% males and FSH was low in 15.3% females. TSH and free T4 was low in 15% and 12.5% patients respectively. IGF-1 was low in only 5% patients. The involvement of pituitary hormones in TBM is not directly related to the disease itself but can occur as a consequence of the infection. Conclusion: The specific impact on pituitary hormone function can vary depending on the severity and duration of the infection, as well as individual factors .


INTRODUCTION
Tuberculosis (TB) is one of the commonest infectious diseases in developing countries like India.TB, caused by the bacteria Mycobacterium tuberculosis, is known to affect almost every organ of our body except hair, nail and enamel.Endocrine involvement in TB is a distinct entity with high incidence in the preantibiotic era.However, although the incidence has reduced now with usage of anti-mycobacterial drugs, still it remains an important clinical entity with post infection sequelae [1].Hypopituitarism has been reported in about 20% of patients, even years after recovery from tuberculous meningitis (TBM) in childhood.Tuberculous lesions affect the hypothalamus, pituitary stalk and directly or indirectly, the pituitary itself [2].The route of spread includes hematogenous and local extension from brain, meninges or sphenoid sinus [1].Apart from anterior pituitary endocrinal dysfunction, TBM also manifests as diabetes insipidus and syndrome of inappropriate ADH secretion (SIADH).Diabetes insipidus is more common in children as compared to adults.It can occur as part of panhypopituitarism [3].It is reported that up to 60% of patients with TBM may present with SIADH or hyponatremia at initial presentation and it is usually reversible with treatment of TB in most cases [4].Thus, pituitary involvement is an important complication of TBM and clinicians should therefore be aware of this entity.

METHODS
The study had a cross-sectional, observational design and was carried out for a period of one year in the inpatient department of a tropical disease institute in India.The study included all cases of 18 to 60 years age of either sex admitted in indoor newly diagnosed as TBM based on Ahuja criteria.Other meningitis due to infective aetiologies were excluded.Those receiving glucocorticoids more than 3 weeks or diagnosed endocrine illnesses or on hormone therapy including oral contraceptives, levothyroxine was excluded.HIV seropositive patients, pregnant or lactating mothers were excluded from the study.
Clinical features of the included cases were noted.Cerebrospinal fluid (CSF) analysis was performed.Pituitary hormone levels were measured using electron chemiluminescent immunoassay.Wherever possible, imaging like Computerized Tomography (CT) scan brain and Magnetic Resonance Imaging (MRI) were done.TBM cases were diagnosed using

DISCUSSION
The involvement of pituitary hormones in TBM is not directly related to the disease itself but can occur as a consequence of the infection.TBM can cause inflammation and damage to the hypothalamus and pituitary gland and play a crucial role in regulating hormone production and release.The specific impact on pituitary hormone function can vary depending on the severity and duration of the infection, as well as individual factors [7].
One of the most common endocrine abnormalities associated with TBM is diabetes insipidus.It occurs due to the damage to the hypothalamus or pituitary gland, resulting in a deficiency of antidiuretic hormone (ADH), also known as vasopressin.ADH helps regulate the balance of water in the body, and its deficiency leads to excessive thirst and increased urine production.TBM can also cause damage to the pituitary glands' corticotroph cells, which produce adrenocorticotropic hormone (ACTH).ACTH stimulates the adrenal glands to produce cortisol, a hormone essential for stress response and metabolism.In cases where the pituitary gland is affected, adrenal insufficiency can occur, leading to low cortisol levels and potentially causing symptoms such as fatigue, weakness, and weight loss.The pituitary gland also produces growth hormone (GH), which plays a vital role in growth, metabolism, and body composition.In some cases of TBM, damage to the pituitary gland can result in growth hormone deficiency, leading to growth retardation in children and potentially affecting metabolism in adults [7].
Aristotelis T et al. studied 16 patients admitted with infectious meningitis.They reported 5 patients (31.25%) to have apparent pituitary hormone deficiencies.Two had gonadotropic and three had somatotropic hormone deficiency [7].
In our study, we found Serum cortisol and ACTH to be low in 20% cases, while serum prolactin was high in 7.5% cases.SIADH was diagnosed in 15% cases.Testosterone was low in 3.7% males and FSH was low in 15.3% females.
A study by Dhanwal et  .TB also appears to be an important, often overlooked cause as reported by various studies and also as found in our cases.
The study has its limitation in being a small sample study with cross-sectional design.Long term follow up could not be done to see for residual hormonal changes and their effects.Moreover, MRI brain with focus on pituitary, couldn't be done in all cases -so, some important radiological finding might have been missed.Also, histopathological changes in the pituitary gland in TBM cases could not be evaluated.Further research should overcome these limitations.

CONCLUSION
TBM patients should undergo pituitary hormone profile and they should also be followed up in order to to avoid any long-term hormonal affection sequelae.Early recognition and treatment are beneficial to prevent such sequelae.

Source of Support: Nil
Conflict of Interest: None Declared.

Ethical Considerations:
The study and its procedures were duly approved by the Institutional Ethics Committee vide approval no CREC-STM/338, and written consent was obtained from all the study subjects' caregiver prior their participation.

HIGHLIGHTS
1. Itself but can occur as a consequence of the infection.The specific impact on pituitary hormone function can vary depending on the severity and duration of the infection, as well as individual factors .
2. Pituitary involvement is an important complication of TBM and clinicians should therefore be aware of this entity .
3. Early recognition and treatment are beneficial to prevent sequelae.

Table 1
[6]Clinical criteria (A)ii.Any one of (B) (C) and (D) SIADH was diagnosed using Schwartz and Bartter Clinical Criterion[6]which includes: i. Serum sodium less than 135mEq/L ii.Serum osmolality less than 275 mOsm/kg iii.Urine sodium greater than 40 mEq/L (due to ADH-mediated free water absorption from renal collecting tubules) iv.Urine osmolality greater than 100 mOsm/kg v. Absence of clinical evidence of RESULTS Out of the 40 TBM cases, 27 were males and 13 females.Categorizing TBM, 2 were definite cases with CSF CBNAAT being positive.10 were highly probable cases, i.e., they met clinical criteria, CSF criteria, radiological criteria and had extra neural involvement.Rest 28 cases were probable as per modified Ahuja criteria, i.e., they had clinical features suggestive of TBM along with any 2 of CSF, radiological and extra neural involvement criteria.Mean age was 31.8 years.All cases were anaemic.(

Table ( 2): Hormonal Profile of TBM Cases Hormonal Profile of TBM cases
al. included 75 TBM cases.They reported 42.7% cases to have relative or absolute cortisol insufficiency.30.7% cases had central hypothyroidism and 49.3% cases had hyperprolactinemia.29.3% cases had multiple hormone deficiencies [8].TSH and free T4 was low in 15% and 12.5% patients respectively in our study.A study by Lam et al., involving 49 cases, reported 10 patients to have abnormal pituitary function.7 of them had growth hormone deficiency [2]. 4 of them also had gonadotropin deficiency [9].More than one hormone disbalance was noted in 9 cases in our study.