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Tuberculosis of endocrine glands in adults and children Ertan Bulbuloglu and Harun Ciralik

INTRODUCTION Tuberculosis is a common disease in the developing world and its incidence is slowly increasing in developed countries. Thus, it is expected that with extrapulmonary TB’s increased prevalence in the world, there is a consequential increase of TB of the endocrine glands. It was recently reported that active TB was present in 871 patients (6.5%) of 13,492 who were autopsied, where extrapulmonary TB was seen in 261 patients (30%).1 The most common endocrine glands involved were the adrenal gland (6.7%), thyroid (1.9%), pancreas (1.5%), ovary (0.9%) and testis (0.3%).1 Thus, TB may affect many of the endocrine glands including the pituitary, thyroid, parathyroid, adrenal pancreas, ovary and testis, which can occur in one of three ways: direct, indirect or due to anti-TB therapy (Table 49.1).2

PITUITARY TUBERCULOSIS EPIDEMIOLOGY Pituitary TB is extremely rare.2–30 Pituitary involvement was observed in 4% of patients with TB in the preantibiotic era,30 while it accounts for approximately 0.15% of all intracranial tumours and 0.6% of all intracranial TB in the postantibiotic era.5,17 Pituitary TB was first reported in 1940 by Coleman et al., although many cases have been reported since then. The atypical and selective involvement of the pituitary gland by Mycobacterium tuberculosis remains unclear.6,10,16,18,23 It is probable that invasion can result by haematogenous spread or directly from basal TB meningitis or paranasal sinus.6,10,15,16,18,24 Common sites associated with pituitary TB are lung, lymph nodes, para-nasal sinus, middle ear and gastrointestinal tract.10,16,18,24,29 Previous or actual TB infection elsewhere was present in only 20 patients in published cases. Among reported cases, the male–female ratio was 26:40 (average age, 34 years for men versus 29 years for women, range 8–55 years). Most cases have been reported from India (40 cases). There have been no reported endocrine TB cases associated with human immunodeficiency virus (HIV). Pituitary TB is extremely rare in children.

SYMPTOMS AND SIGNS Usually dull, continuous and insidious headache and panhypopituitarism are common.2–30 Clinical features of endocrinopathy due to hypopituitarism may be present in patients with pituitary TB.22 Only two acromegaly cases (one with pituitary adenoma) have

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been reported (Fig. 49.1A).14,22 Hyperprolactinaemia (amenorrhoea, infertility, galactorrhoea) is found when the mass compresses the dopaminergic axis.6,8,15 Endocrinological disturbances have been found in 36 out of 56 patients from published cases. Suprasellar extension of pituitary TB commonly manifests with hypothalamic dysfunction and impairment of the visual acuity and fields.2–29 Third and sixth cranial nerve palsy and diabetes insipidus may be seen.16 Rarely, signs of meningitis and confusion can be seen.25,28 Tuberculosis vasculitis may cause atrophic changes in the optic nerves,2,29 and can present as apoplexy-like, with intense headache, sudden neurological deficits like ptosis or visual impairment and altered sensorium.20,30 Alternatively, it may present with pituitary cachexia involving amenorrhoea, asthenia and marked rapid weight loss.15 Erythrocyte sedimentation rate (ESR) may increase and a tuberculin skin test may be positive.16

DIFFERENTIAL DIAGNOSIS Although pituitary adenomas are the most common mass lesions in the sella, the differential diagnosis of pituitary TB from adenomas is difficult. Non-adenomatous sellar lesions are also difficult to diagnose.10,12,16,18,29 In particular, other granulomatous and infectious processes should be considered in the differential diagnosis of pituitary TB.12,13,22,24 Sarcoidosis can infiltrate the pituitary gland and hypothalamus with varying degrees of hypopituitarism and diabetes insipidus, with or without associated symptoms of an intrasellar mass.5,12,22 Giant cell granuloma or granulomatous hypophysitis is a rare disease which can present with a sellar/suprasellar mass and hypopituitarism.5,13,22,24 Histiocytosis X can present with signs of hypopituitarism, diabetes insipidus and an enhancing suprasellar mass, hypothalamic lesions and a thickened stalk on magnetic resonance imaging (MRI).13,22,24 Lymphocytic hypophysitis is a rare, but increasing disorder which affects women in late pregnancy or postpartum period and can present with an enlarging intrasellar or suprasellar mass with varying degrees of pituitary insufficiency.13 Diffuse lymphocytic and plasma cell infiltration of the pituitary can resolve spontaneously in some patients.13,24 For those cases which do not need surgical decompression, conservative followup could be considered.13,24 Infectious pituitary abscesses are rare and can present with symptoms indistinguishable from pituitary tumours, headache, visual disturbances and endocrinopathy.13 Pituitary abscesses may originate from a variety of bacterial organisms and fungal infections.13,18 Signs of systemic involvement or specific imaging findings may provide clues, but surgical biopsy is essential for an accurate diagnosis.13

Table 49.1 Effect of tuberculosis on endocrine glands.. direct, indirect and due to antituberculosis treatment Thyroid

Parathyroid

Adrenal

Pancreas

Testis and ovary

Endocrine abnormalities due to TB of endocrine glands

Sellar mass with/without headache, ophthalmopathy, hypopituitarism. Confirmation tests: MRI/CT scan/ biopsy

Solitary node/multinodular/ mass; painless or painful thyromegaly with or without lymphadenopathy; euthyroid/ hyperthyroidism, abscess/ sinus, etc. Confirmation test: FNAC/ biopsy

Parathyroid gland TB and parathyroid adenoma and primary hyperparathyroidism. Confirmation tests: FNAC/biopsy

Adrenal mass with or without decreased serum cortisol level, increased ACTH level. Confirmation tests: low-dose ACTH stimulation test, CT adrenals with or without FNAC.

Abdominal mass with or without ascites/obstructive jaundice/pancreatic abscess, gastrointestinal bleeding, pancreatitis/secondary diabetes, splenic vein thrombosis. Confirmation tests: CT scan/ USG abdomen FNAC/biopsy

Endocrine abnormalities due to active TB

Hypothalamus–pituitary–adrenal axis is active; growth retardation (following TB meningitis); hyponatraemia without oedema (SIADH); polyuria, polydipsia (diabetes insipidus). Confirmatory tests: clonidine/ insulin tolerance test for GH insufficiency. Plasma osmolality and urinary osmolality for SIADH. Dehydration test for diabetes insipidus

Increased thyroid hormone level

Hypercalcaemia. Confirmatory test: low 1,25 (OH)2 D3 and low parathormone

Increased cortisol level. Adrenal enlargement

Adnexal mass with or without abdominal pain/ infertility/menstrual abnormalities/ascites/ raised serum CA125. Confirmatory test: MRI, CT scan/biopsy. Scrotal mass with or without painless or painful abscess/fistula/ azoospermia. Confirmation tests: USG FNAC/biopsy. Gonadal dysfunctions, decreased dehydroepiandrosterone and testosterone levels; hypogonadotropic hypogonadism increased oestradiol and prolactin level

Thyroid binding globulin rises (with rifampicin, isoniazid, pyrazinamide); thyronine response unit decreases; goitrogenic (with para-amino salicylic acid)

Masks hypercalcaemia and hypercalciuria

Increases steroid metabolism; precipitates Addisonian crisis

Anti-TB therapy interacts adversely with oral antidiabetic therapy; insulin resistance

Failure of oral contraceptives

Effect of anti-TB therapy on endocrine system

ACTH, adrenocorticotropic hormone; CT, computed tomography; FNAC, fine needle aspiration cytology; GH, growth hormone; MRI, magnetic resonance imaging; SIADH, syndrome of inappropriate antidiuretic hormone secretion; USG, ultrasound-guided. Adapted from Arya (1999).2

Tuberculosis of endocrine glands in adults and children

Pituitary

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Fig. 49.1 (A) Preoperative MRI of sella shows a macroadenoma. (B) Haematoxylin þ eosin stain. Arrow: granuloma; short arrow: adenoma cells. Gazioglu N, Ak H, Oz B, et al. Silent pituitary tuberculoma associated with pituitary adenoma. Acta Neurochir 1999;141(7):785–6.

INVESTIGATIONS Radiological findings are rarely characteristic and it is difficult to differentiate pituitary TB from sellar lesion-like adenoma.6–30 Radiological features such as leptomeningeal enhancement and other parenchymatous brain tuberculomas are helpful in diagnosing pituitary TB.16 Intrasellar TB on computed tomography (CT) appears as an iso- to hyperdense mass which enhances brilliantly after contrast administration. Rarely they may present with peripheral ring enhancement.16,18,29 Contrast MRI characteristically demonstrates thickened infundibulum and hypophyseal stalk. Pituitary haemorrhage, abscess, adenoma and calcification are rarely shown.16,18,29 Suprasellar extension is more common than sphenoid sinus, nasopharynx or cavernous sinus invasion in pituitary TB.16 Hydrocephalus is uncommon but may be present with TB meningitis.28 Chest and head radiograph may be used.15,16,19 Polymerase chain reaction (PCR) was positive in only two cases; one was from pituitary tissue and the other from cerebrospinal fluid (CSF).13,23

blood–brain barrier effectively, regardless of the presence of inflammation. Duration from at least 3 months to 2 years has been proposed.6–13,15–30 If isolated pituitary TB is removed completely, anti-TB therapy is unnecessary.14 If there is pituitary TB with adenoma, anti-TB therapy may be given after radiotherapy.15 Three out of 56 patients died during treatment. Hormone serum levels should be monitored.

COMPLICATIONS If surgery is carried out by a skilled surgeon, complications can be minimal; however, transient or permanent diabetes insipidus, CSF rhinorrhoea,12 monohormonal or polyhormonal deficiencies5 and visual field defects26,29 have been known to occur.

TUBERCULOSIS OF THE THYROID GLAND EPIDEMIOLOGY

PATHOLOGY There has been evidence of necrotizing and non-necrotizing granulomatous inflammation (Fig. 49.1B). Acid-fast bacilli (AFB) are rarely seen and were observed in only one case at histopathology.15

MANAGEMENT Management should include appropriate hormonal replacement, especially cortisol, thyroxine, antidiuretic and gonadal hormones, and comprehensive anti-TB therapy and surgery.7,15,30 The role of surgery in pituitary TB is tissue diagnosis and decompression.15,16,18,29 Early surgical decompression of pituitary TB with apoplexy-like appearance prevents persistent neuro-ophthalmic deficit.30 Although a subfrontal approach for excision is recommended,2,4 the preferred route is the transsphenoidal route,5–22 which prevents CSF contamination by TB material.15,16,29 Although response to anti-TB therapy in pituitary TB is good, there is no agreement on regimen and duration of this treatment.6–30 A combination of bactericidal drugs such as rifampicin, isoniazid, pyrazinamide and streptomycin is preferred as they penetrate the

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Tuberculosis of the thyroid gland is a rarely encountered condition even in countries with a high TB prevalence,31–37 and was considered non-existent in the middle of the nineteenth century. Thyroid TB was first recognized on autopsies of thyroid in symptom-free miliary TB cases in 1862 by Lebert.31–34 Bruns reported the first clinical case of primary thyroid TB in 1893.31,33,34 Coller and Huggins described five cases in 1926 in a series of thyroid-operated patients.31–34 Thereafter, sporadic cases have been reported, the majority being discovered at postmortem examinations during the past decade. Up to now there have been 73 cases published in the English literature.32 Thyroid TB rates are 0.1–0.003%, 0.2% and 14% in postmortem studies, chronic thyroiditis specimens and miliary TB, respectively.33 However, its true incidence is unknown. The rarity of this entity is not clear but could be explained by colloid material possessing bactericidal action, extremely high blood flow and an excess of iodine, enhanced destruction of tubercle bacilli by increased physiological activity of phagocytes in hyperthyroidism or anti-thyroid binding capacity roles of thyroid hormones.32–34

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Thyroid TB may be primary or secondary to other sites.31–37 During the past decade, the increasing incidence of extrapulmonary forms was reportedly greater than that of the pulmonary forms alone. Of the 73 cases reported in the literature, only 11 had associated pulmonary forms.32 Infection spreads to the thyroid by the lymphogenous or haematogenous route or directly from adjacent organs.32–34 According to studies on thyroid TB, there is a slight female predominance. The ages of patients reported have ranged from 9 to 83 years, with a median age of 40 years for men and 43 years for women.34 There has been a case report of a 9-year-old patient but no known HIV-infected case.32

SYMPTOMS AND SIGNS The diagnosis of thyroid TB is difficult since there is not any specific symptom. It may be asymptomatic or may present with non-specific manifestations.32–37 It may be seen as an isolated nodule or as a diffuse or multinodular goitre.32–37 The presence of satellite adenopathy may indicate malignant aetiology, and an abscess or chronic sinus may also be present.32–34,37 The symptoms of mass effect such as dysphagia or transient paralysis may be found.32–34,37 Hyperthyroidism due to parenchymal damage and increased release of thyroid hormones may be seen, whereas hypothyroidism is seen as a result of total destruction of the gland.32–37 Thyroid TB has been known to cause pyrexia of unknown origin or lethargy, and can mimic cancer or thyroiditis.32–37 Although normal thyroid function is the most frequent laboratory finding, thyroid function abnormalities may also be seen. Only five cases have been reported with thyrotoxicosis.32 A high ESR and a positive tuberculin skin test may suggest the tuberculous aetiology.32–37

INVESTIGATIONS Fine needle aspiration cytology (FNAC) is a useful method for diagnosing thyroid TB despite a paucity of evidence in the literature.32–37 Thyroid TB was diagnosed by FNAC in 0.6–1.15% of cases with thyroid lesions.37 Nearly half of reported cases have been diagnosed with FNAC, and the diagnosis must be substantiated by histopathological findings and/or identification of AFB.32,36 CT scan and ultrasonography (US) may be useful.36

DIFFERENTIAL DIAGNOSIS Thyroid TB should be distinguished from thyrotoxicosis, acute thyroiditis, thyroid cancer, Riedel thyroiditis and thyroid nodules.32–37 Lymphocytic infiltration and granulomas may also be seen in sarcoidosis, subacute thyroiditis and autoimmune thyroiditis.33–37 The most distinct feature of subacute thyroiditis is the giant cell granuloma, its resemblance to the granulomatous tissue reaction in thyroid TB causing the term pseudotuberculous thyroiditis to become more widespread.33,34,37 Sometimes thyroid TB is mistaken for carcinoma.33 However, there have been reports of TB thyroiditis coexisting with thyroid carcinoma in the same patient.34 A differentiation from thyroid cancer is essential to avoid unnecessary thyroid surgery.32,33

PATHOLOGY Morphological variations of thyroid TB include multiple tubercles in cases of miliary TB, solitary and merging tubercles, caseation

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necrosis or cold abscesses, and cicatrized tuberculous foci.32–34 The histological diagnosis is based on the presence of epithelial cell granulomas with peripheral lymphocytic cuffing, Langhans giant cells and central caseation necrosis.32–37 Rarely, AFB has been observed at histopathology.32,34

MANAGEMENT Following diagnosis, surgery has a limited role with surgical removal of the affected parts of the thyroid gland or surgical drainage.32–37 If surgery is required, early anti-TB drugs remain the keystone of treatment, avoiding total destruction of the thyroid gland and consequentual hypothyroidism.32–37 Thyroid hormone serum levels should be monitored.32,34 Although no specific study on the efficacy of the various regimens of thyroid TB treatment has been conducted, the same regimens can be used effectively in thyroid as used in any other extrapulmonary TB.36 If the affected thyroid gland is removed, there is no need for treatment.32

COMPLICATIONS Despite adequate treatment, recurrence and failure rates are about 1% owing to drug-resistant TB. When hypothyroidism occurs, treatment is directed according to thyroid-stimulating hormone levels.32

TUBERCULOSIS OF PARATHYROID GLAND EPIDEMIOLOGY Tuberculosis of the parathyroid gland is very rare even in countries with a high TB prevalence. Primary parathyroid TB is unknown, but coexistence of TB with adenoma in parathyroid glands has been reported.38,39 Two cases of parathyroid gland involvement from adjacent thyroid lobe and lymph nodes have also been reported.38,39 Parathyroid TB is expected to result in the gland’s hypofunction, as granulomatous inflammation of endocrine glands has almost invariably the same result. However, these two cases had hyperfunction, which could be explained by a pre-existent parathyroid adenom or that not all parathyroid glands are affected by TB inflammation in the same manner.38,39 Tuberculosis organisms may spread from an adjacent focus or distant haematogenous dissemination.38,39

SYMPTOMS AND SIGNS Symptoms and signs are shown in Table 49.2. Patients with parathyroid TB may manifest constitutional symptoms such as fever, anorexia, weight loss, malaise and fatigue and/or hyperparathyroidism due to adenoma in parathyroid glands.38,39

DIFFERENTIAL DIAGNOSIS Primary hyperparathyroidism is common in industrialized nations, while rates of detection have increased in developing nations. Likewise, TB is a problem in both industrialized and developing nations. Thus, we will probably see more coexistence of these two diseases in same population. Hypercalcaemia is a common electrolyte disorder and primary hyperparathyroidism, granulomatous diseases and malignancies are the most common in aetiology.38,39 A patient with two concurrent underlying diseases

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Table 49.2 Symptoms and signs of tuberculosis of the parathyroid gland Reference

Age/ sex

Symptoms, signs and tests

Investigations

Tuberculosis elsewhere

Endocrinology before/after treatment

Surgery

Jakob et al.38

35/F

Generalized body ache, increased serum calcium and parathormone

Thyroid lobe

Kar et al.39

36/F

Generalized bone ache, anaemia, muscular weakness, increased serum calcium and parathormone

Subperiosteal bone resorption, MIBI scintigraphy Ultrasonography and CT scan, chest radiograph

Primary hyperparathyroidism/ symptom free Primary hyperparathyroidism/ symptom free

Parathyroidectomy with adjoining right thyroid lobe Parathyroidectomy with adjoining right lymph nodes

capable of causing hypercalcaemia is rare and poses both a diagnostic and therapeutic challenge. Also, the mass, abscess, inflammation and malignancy of the neck region are important in differential diagnosis.

Lymph node

There was non-necrotizing granuloma in the parathyroid tissue and lymph node of one patient and necrotizing granuloma in the parathyroid tissue of another patient, with parathyroid adenoma in both of them.38,39

metastatic neoplasia, haemochromatosis and congenital adrenal hyperplasia–adrenoleucodystrophy.42–44 A study has shown interestingly that 11% of patients with adrenal TB had antibodies.45 Adrenal TB is an uncommon clinical condition, and adrenal dysfunction as a result of TB is a rarer combination.41–45 Although only 0.03% involvement of adrenal gland has been reported in extra-adrenal with extrapulmonary TB,46 it remains the most commonly involved endocrine organ in TB.46–48 In one study of patients with active TB, endocrine TB involvement was 9.5%, adrenal gland involvement 6.5% and single organ involvement 25%.48 The primary source of TB is usually the lung.46–48 Postmortem studies usually confirm that TB may exclusively involve the adrenal glands.46–48 Nevertheless, despite advances in diagnostic techniques, premortem diagnosis of isolated adrenal TB remains extremely rare, and has been reported in only six studies.46–51 Adrenal TB is extremely rare in children. Male predominance and a mean age of 61 years have been reported.1 In HIV-infected patients adrenal insufficiency and adrenal gland involvement by Mycobacterium avium–intracellulare and M. tuberculosis is more commonly seen. However, the risk of adrenal insufficiency is not increased in coinfected patients.52

MANAGEMENT

SYMPTOMS AND SIGNS

In both patients, diagnosis was made with histological examination of surgically removed tissue. The patients were given triple antiTB treatment for the first 3 months and then a two-drug regimen for 3 months for the first patient and 6 months for the other. Outcome was good in both patients.38,39

It is believed that > 90% of the adrenal gland must be destroyed before the clinical features of adrenal insufficiency are manifested.50,51,53 Active pulmonary TB may be associated with Addison’s disease characterized by enlarged adrenal glands, with or without normal adrenocortical functions.53 Because it is frequently unrecognized in its early stages, Addison’s disease due to TB can present with chronic adrenal insufficiency and rarely with lifethreatening acute adrenal insufficiency.50,51–53 Also, TB-related sudden death has been reported.54 However, when coexisting with Cushing’s syndrome, the typical symptoms related to Cushing’s syndrome might be partially masked by the adrenal insufficiency as a result of adrenal TB.55 Addison’s disease due to adrenal TB may manifest with diverse and non-specific clinical and/or biochemical features (Table 49.3).

INVESTIGATIONS Biochemical parameters (serum calcium, alkaline phosphatase, parathyroid hormone phosphorus, etc.), ultrasonography, CT scan, MIBI scintigraphy, bone radiograph and bone densitometry could show primary hyperparathyroidism and complications. Chest radiography, tuberculin skin test and ESR may be useful. PCR, FNAC and AFB may help to diagnose TB.38,39

PATHOLOGY

ADRENAL TUBERCULOSIS EPIDEMIOLOGY Primary adrenal insufficiency (Addison’s disease) is a rare endocrine disease in which there is destruction of the adrenal cortex with resultant inadequate secretion of the adrenal cortical hormones – cortisol, aldosterone and androgens.41–43 The prevalence of Addison’s disease has been reported to be 39–110 per million population.42,43 The commonest causes of Addison’s disease are autoimmune disease and adrenal TB.41–43 Between 1930 and 1950, adrenal TB accounted for 70–80% of cases of Addison’s disease.44 Currently in developed countries, idiopathic adrenal atrophy is responsible for 68–94% of the cases and adrenal TB for 18–30% of the remaining cases.45 In contrast, in developing countries, the most common cause of Addison’s disease is TB.41–45 Others are fungal infection,

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DIFFERENTIAL DIAGNOSIS Other causes of adrenal insufficiency as well as atrophy, calcification and mass lesions of the adrenal gland are important in the differential diagnosis.44,46,51 Primary adrenal insufficiency is almost certainly present when a high corticotropin (ACTH) level is associated with a low cortisol response to ACTH challenge.56 Low levels of plasma ACTH indicate secondary (pituitary) or tertiary (hypothalamic) causes that can

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Table 49.3 Presented symptoms, signs and biochemical abnormalities due to adrenal tuberculosis Symptom

Sign

Biochemical abnormality

Fatigue Muscular weakness

Postural hypotension Sinus tachycardia Weight loss Extra-adrenal TB source signs Generalized pigmentation, darkened skin creases, pigmented buccal mucosa and nail beds

Decreased cortisol level Low ACTH-stimulated cortisol responses Hyponatraemia, hyperkalaemia, hypoglycaemia, eosinophilia

Malaise Abdominal pain Vomiting Diarrhoea Behaviour changes Headache Sweating

Lymphocytosis Increased erythrocyte sedimentation rate and C-reactive protein level

Fever Positive tuberculin skin test (PPD) Associated thyroiditis

be differentiated by corticotropin-releasing hormone (CRH)stimulation testing. ACTH and aldosterone levels are also helpful in distinguishing primary from secondary adrenal insufficiency.56 CT and MRI are important in the differential diagnosis of primary adrenal insufficiency. Typically, autoimmune adrenal insufficiency is associated with atrophy of the adrenal glands, whereas disorders such as TB, fungal infections, amyloidosis, bilateral haemorrhage, primary tumour and metastatic disease are associated with adrenal enlargement.48,49 Long-standing TB, however, may also cause adrenal atrophy and calcification.50 Similar findings have been described with adrenal blastomycosis and histoplasmosis, but TB is rarely unilateral. Tuberculosis should still be considered in the aetiology of adrenal insufficiency, particularly in endemic areas.40–42 Adrenal TB or other causes may be identified by percutaneous needle biopsy of an enlarged adrenal gland.43–49 The finding of incidental masses in the adrenals has increased (from 0.35% to 5% of patients) in recent decades with the increased usage of CT and MRI. These are excellent methods for detecting an adrenal mass, but percutaneous biopsy could be required to differentiate lesions except myelolipomas, cysts, haemorrhages, phaeochromocytomas and adrenal metastases.43,49

INVESTIGATIONS Specific diagnostic tests should be performed when symptoms or signs suggest the possibility of Addison’s disease with TB, e.g. decreased serum cortisol level; however, a single normal serum cortisol level does not rule out Addison’s disease, although a high value would make the diagnosis very unlikely. The low-dose ACTH stimulation test using 1 mg of ACTH has been used to diagnose subclinical adrenal dysfunction.40–43,48,53 CT scan of the abdomen in adrenal TB shows typical features of shrunken and calcified adrenals (Fig. 49.2A) in the chronic stage and enlarged in the active stage (Fig. 49.2B).43,49 A normal CT finding is also possible in a biochemically proven case of Addison’s disease.15 MRI signs of adrenal TB are usually of bilateral, but asymmetrical enlargement. They tend to be heterogeneous with low attenuation areas of caseating necrosis and calcification.43,49,51 FNAC may be used to confirm the diagnosis of adrenal TB in acute cases.49,51 Bacteriological techniques and PCR could be used in some doubtful cases. A positive tuberculin skin test result would suggest TB but require further investigation. Radiography could show adrenal calcification or another focus in the lung.46,53

Increased urea nitrogen level and creatinine Hypercalcaemia

PATHOLOGY Adrenal TB shows necrotizing granulomatous inflammation including epithelioid histiocytes, giant cells and caseous necrosis. Sometimes bacilli can be evident. Caseous necrosis has been found in about 70% of cases, and thus is an important sign for the diagnosis of adrenal TB.1 However, typical granulomatous inflammation with Langhans giant cells has been found in less than half of cases, which may be related to the local suppressive effect of steroids secreted into the adrenal cortex. If Addison’s disease occurs, Langhans giant cells are more commonly seen (Fig. 49.2C).1,46,53

MANAGEMENT Treatment of acute adrenal insufficiency must not be delayed. High doses of intravenous steroids and fludrocortisone should be given.46,53,56 Intravenous doses may be replaced by oral maintenance doses in 3–5 days.46,53,54 Antituberculosis therapy is common practice for treating patients with TB–Addison’s disease for 1 year with isoniazid for inactive TB.15 However, the dual and triple (isoniazid (5 mg/kg), rifampicin (10 mg/kg) and pyrazinamide (25 mg/kg)) therapies are given for 12– 18 months.46,48,53 Antituberculosis therapy is known to increase the degradation of corticosteroids. Initiation of anti-TB therapy may lead to overt manifestations of subclinical adrenocortical insufficiency. Addisonian crisis has also been reported with the initiation of rifampicin therapy.56 Corticosteroids can cause immunosuppression and exacerbation of old TB foci.56 Significant increases in catecholamine levels with the severity of the disease suggest that the stress of infection plays a role in induction of enzymes responsible for catecholamine synthesis with subsequent stimulation of ACTH and cortisol synthesis.56 Patients should have regular follow-up visits with 3-month intervals.53 Addison’s disease due to TB is usually irreversible.46,46,53 Except for a few cases most studies have shown no improvement in adrenal corticosteroid production after anti-TB treatment.53,57 Histopathological evaluation of resected bilateral adrenal glands revealed no remaining vital adrenal tissue.1,53,57 Thus improvement after anti-TB therapy could not be expected.53,57 However, it is unclear whether anti-TB therapy prevents adrenocortical failure in the patients with enlarged adrenal glands but normal adrenal function.53,57 Obviously, diagnosis of this kind of abnormality is very difficult to make unless adrenal imaging is routinely performed.53,57 Therefore, prospective studies are needed to determine the effectiveness of anti-TB therapy in patients with normal

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Fig. 49.2 (A) Calcified adrenals on CT. (B) Lobulated, right adrenal depicting a 6  3.5  2 cm homogeneous mass and left adrenal gland showing a nodular irregularity. (C) Histopathological evaluation of the resected material. Large areas of caseous necrosis and granulomatous inflammation comprising Langhans giant cells and epithelioid histiocytes in adrenal tissue. Serter R, Koc G, Demirbas B, et al. Aral Acute adrenal crisis together with unilateral adrenal mass caused by isolated tuberculosis of adrenal gland. Endocr Pract. 2003 Mar-Apr;9(2):157–61.

adrenal function or subclinical adrenal failure and enlarged adrenal glands due to non-viable necrotic and caseous tissue.53

PANCREATIC TUBERCULOSIS EPIDEMIOLOGY Pancreatic TB is a rare entity in developed countries, occurring mostly in the setting of HIV infection or immunosuppression for transplantation.58–61 There has been an increase in the number of

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immunocompetent patients, originating mostly from developing countries.58–61 In a large portion of those cases, there is neither concomitant disease elsewhere nor evidence of miliary dissemination.58 Moreover isolated pancreatic TB is of lesser prevalence. The most common location of a pancreatic mass has been reported in the head or body; however, occasionally isolated involvement of the pancreatic tail has also been described.62 The pancreas is in the retroperitoneum and protected from direct environmental exposure. Purified lipases, pancreatic extracts and DNAses appear to have antimycobacterial effects.63 Thus, the pancreas is relatively

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resistant to mycobacterial invasion.63 The true incidence of pancreatic TB is unknown. In a MEDLINE search for English language articles from 1966 to 2004 using the MeSH terms ‘tuberculosis’ and ‘pancreas’ a total of 116 reports of pancreatic TB were identified in immunocompetent individuals worldwide.64 Mean age range was 40–45,64 and there was a slight male predominance.65 In another study 14 out of 62 cases (23%) were HIV-infected.66 Forms of mycobacterial infection of the pancreas have been described as: 1. miliary TB (M. tuberculosis); 2. spread to the pancreas from coeliac and other retroperitoneal lymph nodes (M. bovis); 3. primary localized pancreatic TB due to M. tuberculosis, which may reflect a point of origin from the intestinal tract;67,68 and 4. toxic-allergic reaction of the pancreas in response to TB elsewhere.69

SYMPTOMS AND SIGNS Common symptoms are abdominal pain (75%), anorexia with weight loss (69%), fever and night sweats (50%) and back pain and jaundice (31–40%).64–66 Infrequently, pancreatic TB may present as acute pancreatitis with radiographic findings.64–66 Other rare manifestations include obstructive jaundice, gastrointestinal bleeding via direct invasion of a peripancreatic artery, pancreatic abscess, chronic pancreatitis, diabetes, a pancreatic mass mimicking malignancy, pancreatic abscess, splenic vein thrombosis and ascites.64–66 Iron deficiency anaemia, lymphocytopenia, elevated transaminases and alkaline phosphatase have been seen in approximately 50% of cases.64–66 Most patients have a high sedimentation rate and C-reactive protein and the tuberculin skin test has been positive in over two-thirds of cases.61

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carcinoma.74 There are no pathognomonic CT features of TB, although ‘ring enhancement’ or low-density areas within enlarged lymph nodes is accepted as a characteristic feature.73 Associated findings may include splenic vein thrombosis, focal hepatic or splenic lesions, bowel thickening in the ileocaecal region and ascites.71–73 Calcification in the gland has been reported in pancreatic TB.75 Chest radiography and sputum smears for AFB are mostly negative. Endoscopic retrograde cholangiopancreatography (ERCP) may show displacement and stenosis of the main duct or involvement of the common bile duct leading to intrahepatic biliary dilatation.64,74 The success rate of image-guided percutaneous FNAC or biopsy in diagnosing pancreatic TB is less than 50%.64,65 Endoscopic ultrasound FNA cytology/biopsy has proved to be an excellent tool for the cytological diagnosis of pancreatic and peripancreatic masses.64,65 However, the potential risk of tumour dissemination sometimes prevents physicians from performing FNAC. Although spillage of tumour cells by FNAC has not been reported, PCR has proved important for rapid diagnosis. Also, PCR of ascites has been reported.64,65 Laparoscopy might prove helpful if TB cannot be confirmed by FNAC or core biopsy. However, the diagnosis has been made in most cases by laparotomy or at necropsy.64,65 Also, it appears hypointense on fat-suppressed T1-weighted images and hyperintense on T2-weighted images, and shows heterogeneous enhancement after Gd-DTPA injection on MRI.75

PATHOLOGY The presence of caseating granulomatous inflammation with or without necrosis is the commonest finding on histopathological examination. Caseating granulomas are seen in 75–100% of cases.64 AFB are identified in only 20–40% of cases.64

MANAGEMENT DIFFERENTIAL DIAGNOSIS Pancreatic TB may be especially confused with carcinoma of the pancreas. There are no clear differences in the radiological appearances of cystic neoplasm and TB abscess of pancreas; both have septa within the mass, cyst with internal echoes and nearby hypodense lymphadenopathy.71 A calcified rim of cyst wall and mural nodulars are characteristic findings for cystic neoplasms, but these may occasionally be present in TB.70,71,73 A diagnosis of TB can be suggested only in the presence of ancillary findings such as pulmonary TB, pleural effusion, enlarged coeliac lymph nodes, lesions in other solid viscera, ascites, mural thickening in the ileocaecal region or a positive tuberculin skin test.71 Interestingly abdominal pain is more frequent at the time of presentation with pancreatic TB than with pancreatic cancer. The presence of fever with a pancreatic mass favours TB; however, non-Hodgkin’s lymphoma should also be considered in this clinical scenario. A firm diagnosis can only be made with the help of histopathological or microbiological evidence of the disease. Most patients have been diagnosed at laparotomy or FNAC. Another diagnostic option is initiating treatment with anti-TB therapy and evaluating the response to therapy.71,72

INVESTIGATIONS Ultrasound and CT scan may show a diffusely enlarged pancreas, a mass lesion, or focal hypoechoic or hypodense lesions usually in the pancreatic head region.74 These finding are non-specific and may be seen with focal pancreatitis of any aetiology, such as in pancreatic

Response to anti-TB therapy is very favourable.58–62,66 The most frequently used combinations were isoniazid/rifampicin/ pyrazinamide/streptomycin or ethambutol and isoniazid/rifampicin/ streptomycin (older studies).62,64–66 The duration of the therapy was usually 6–12 months.58–66 Recurrences are rare. Laparotomy should be indicated to establish a diagnosis in most of the suspected cases. Other indications for an exploration are secondary complications, such as compression of common bile duct, or gastrointestinal bleeding. The role of resection (e.g. pancreatoduodenectomy) is very limited. Imaging-guided drainage may be useful in cases that present with an abscess.58,62,64

TUBERCULOSIS OF TESTIS EPIDEMIOLOGY Epididymo-orchitis is a rare manifestation of genital TB which usually results from retrograde infection from prostate and seminal vesicles.77–82 The infection affects epididymis first, then testis is usually involved by direct spread.77–82 Rarely it may be caused by haematogenous dissemination, bacillus Calmette–Gue´rin (BCG) and venereal transmission.77–82 Also, isolated testicular TB is extremely rare. Men aged 20–50 years are affected most commonly.80 Isolated testis involvement with ectopic testis has been reported in children.82 Testicular TB in patients with acquired immunodeficiency syndrome is rarely seen.82

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SYMPTOMS AND SIGNS Testicular TB presents with a painless or slightly painful scrotal mass.77–82 The presence of an abscess or scrotal sinus formation should alert the clinician to TB, especially as such sinus tracts are known to occur as a result of caseous material reaching the scrotal skin; thus a chronic draining sinus should be regarded as having a tuberculous origin until proven otherwise. Patients may have systemic manifestations such as fever and sweats. Chest radiographs have failed to reveal any active pulmonary disease and urine analysis and a plain abdominal radiograph excluded tuberculous infection of urinary tract.77–82

DIFFERENTIAL DIAGNOSIS Testicular tumours, acute infections, infarction, granulomatous orchitis and testicular TB should be considered. The presence of epididymal involvement in conjunction with a testicular lesion is suggestive of an infection rather than a tumour, because testicular TB is nearly always caused by epididymitis. Sometimes the epididymides may be enlarged because of coincidental epididymitis or direct tumour invasion – especially in lymphoma, but also in germ cell tumours. Skin thickening and a large volume of peritesticular fluid tend to indicate a non-neoplastic process. Differentiating TB epididymitis from non-tuberculous epididymitis is important for disease management. Generally, the sonographic findings of non-tuberculous epididymitis consist of diffuse enlargement of the epididymis and a uniform decrease in its echogenicity. Heterogeneous enlargement of the epididymis may distinguish TB from non-tuberculous epididymitis. Also, Doppler sonography may show more signal tuberculous orchitis rather than non-tuberculous orchitis.77–82

The ultimate prognosis is determined by the degree of systemic illness.

TUBERCULOSIS OF OVARIES EPIDEMIOLOGY The tubes are almost always involved in TB of the female genital tract, but the ovarian parenchyma is affected in only 9–11% of cases. Ovarian involvement appears to be fairly common in developing countries and may be usually due to haematogenous or lymphatic spread and occasionally to peritoneal dissemination.83,84 Isolated ovarian involvement is extremely rare.83

SYMPTOMS AND SIGNS Tuberculosis of ovaries in the absence of endometrial and tubal involvement can pose problems in diagnosis. Patients may present with non-specific lower abdominal pain, infertility, menstrual abnormalities, abdominal distension, ascites, and postmenopausal and intermenstrual bleeding. Systemic constitutional symptoms of weight loss, feeling unwell and night sweats may be present. Involvement of the ovaries may result in a unilateral or bilateral adnexal ovarian mass. Fistula formation to the bowel, skin or vagina may be seen. An adnexal mass and a raised serum CA125 level can be mistaken for ovarian cancer and can result in unnecessary surgical intervention.83 Pelvic examination may reveal mass or ascites. ESR is usually raised.83 A tuberculin skin test may be helpful.83 Chest radiography is aimed at demonstrating current or past tuberculous lesions in the lungs. Tuberculosis peritonitis may accompany TB of the ovaries. The definite diagnosis is usually made postoperatively.83,84

INVESTIGATIONS Scrotal US is helpful in assessing for complications of testicular TB, such as fistula or abscess formation.80 The most characteristic US pattern of testicular TB is the presence of heterogeneously or homogeneously nodular and multiple small hypoechoic nodules in an enlarged testis. Scrotal skin thickening, scrotal abscesses and scrotal sinus tract are other US features. Colour Doppler sonography may help in the diagnosis.77–82 A renal US for evaluating the upper tracts for evidence of TB is also warranted. FNAC is very successful for diagnosis of TB.77–81

DIFFERENTIAL DIAGNOSIS Acute and chronic bacterial pelvic infections, sarcoidosis, Crohn’s disease, actinomycosis, leprosy, granuloma inguinale, lymphogranuloma venereum, syphilis, histoplasmosis, brucellosis, berylliosis silicosis, tularaemia, foreign body reaction, other intra-abdominal diseases and rarely schistosomiasis and filariasis should be kept in mind.83,84

INVESTIGATIONS PATHOLOGY The diagnosis of TB depends upon the demonstration of epithelioid granuloma, necrosis and/or AFB.77–82

COMPLICATIONS Complications of advanced testicular TB are scrotal abscess and fistula formation. Severe immunosuppression increases that complication. Both complications are usually treated by scrotal surgery. If epididymis is affected, patients may become infertile, because of either extensive duct destruction or obstruction of the vas deferens.77–82

TREATMENT Standard short-course anti-TB treatment is usually sufficient.77 Ulcerative lesions and sinus could improve in the seventh month.77

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MRI, CT scan and US are helpful. Cystic or both solid and cystic adnexal masses, unilateral or bilateral, are accompanied by ascites, omental or mesenteric infiltrations and peritoneal thickening. These findings closely resemble those of peritoneal carcinomatosis from ovarian cancer. Calcifications may be found in adnexal masses and suggest TB, but are not frequently observed, especially in active inflammation. Lymph node enlargement and dense adhesion with the adjacent organs is common, and the latter may reflect a late fibrotic process of this infection. Loculated fluid collections with internal septations are often found adjacent to the masses or in the cul-de-sac. Laparoscopic findings may include ovarian mass, adhesions, tubal abnormalities and ascites. Tissues of ovaries can be obtained at laparoscopy or laparotomy for culture and PCR. If the patient does not have tubal involvement, hysterosalpingogram may not reveal a typical tubal pattern.83,84

CHAPTER

Tuberculosis of endocrine glands in adults and children

PATHOLOGY Microscopy demonstrates the typical caseous granulomatous lesions with giant epithelioid cells. AFB can provide a quick diagnosis.83,84

49

in isolated TB of the ovaries. If it is not isolated, therapy is the same as that for genital TB. Surgery should be recommended in persistent disease, multidrug resistance or coexistence with malignancy.83,84

MANAGEMENT

COMPLICATIONS

First, three- or four-drug therapy for 2 months and maintenance with ethambutol and streptomycin for 4 months is recommended

Patients may present with infertility, menstrual abnormalities, ascites, and hydronephroses.83

REFERENCES 1. Lam KY, Lo CY. A critical examination of adrenal tuberculosis and a 28-year autopsy experience of active tuberculosis. Clin Endocrinol 2001; 54(5):633–639. 2. Arya V. Endocrine dysfunctions in tuberculosis. Int J Diab Dev Countries 1999;19:71–77. 3. Oliver LC. A pituitary tuberculoma. Lancet 1952; 1(14):698–699. 4. Brooks MH, Dumlao JS, Bronsky D, et al. Hypophysial tuberculoma with hypopituitarism. Am J Med 1973;54(6):777–781. 5. Eckland DJ, O’Neill JH, Lightman SL. A pituitary tuberculoma. J Neurol Neurosurg Psychiatry 1987;50:360–361. 6. Esposito V, Fraioli B, Ferrante L, et al. Intrasellar tuberculomas: case report. Neurosurgery 1987; 21:721–723. 7. Delsedime M, Aguggia M, Chiado Cuttin I, et al. Isolated hypophyseal tuberculoma: case report. Clin Neuropathol 1988;7:311–313. 8. Taparia SC, Tyagi G, Singh AK, Gondal R, Prakash B. Sellar tuberculoma. J Neurol Neurosurg Psychiatr 1992;55:629. 9. Ghosh S, Chandy MJ. Intrasellar tuberculoma. Clin Neurol Neurosurg 1992;94:251–252. 10. Ranjan A, Chandy MJ. Intrasellar tuberculoma. Br J Neurosurg 1994;8:179–185. 11. Pereira J, Vaz R, Carvalho D, et al. Thickening of the pituitary stalk: a finding suggestive of intrasellar tuberculoma? Case report. Neurosurgery 1995; 36:1013–1016. 12. Petrossians P, Delvenne P, Flandroy P, et al. An unusual pituitary pathology. J Clin Endocrinol Metab 1998;83:3454–3459. 13. Ashkan K, Papadopoulos MC, Casey AT, et al. Sellar tuberculoma: report of two cases. Acta Neurochir (Wien) 1997;139:523–525. 14. Gazioglu N, Ak H, Oz B, et al. Silent pituitary tuberculoma associated with pituitary adenoma. Acta Neurochir (Wien) 1999;141:785–786. 15. Basaria S, Ayala AR, Guerin C, et al. A rare pituitary lesion. J Endocrinol Invest 2000;23(3):189–192. 16. Sharma MC, Arora R, Mahapatra AK, et al. Intrasellar tuberculoma: an enigmatic pituitary infection: a series of 18 cases. Clin Neurol Neurosurg 2000;102(2):72–77. 17. Sinha S, Singh AK, Tatke M, et al. Hypophyseal tuberculoma: direct radiosurgery is contraindicated for a lesion with a thickened pituitary stalk: case report. Neurosurgery 2000;46:735–738. 18. Patankar T, Patkar D, Bunting T, et al. Imaging in pituitary tuberculosis. Clin Imaging 2000;24(2):89–92. 19. Manghani DK, Gaitonde PS, Dastur DK. Pituitary tuberculoma: A case report. Neurol India 2001; 49:299–301. 20. Kumar N, Singh S, Kuruvilla A. Pituitary tuberculoma mimicking adenoma: magnetic resonance imaging. Australas Radiol 2001;45:244–246. 21. Arunkumar MJ, Rajshekhar V. Intrasellar tuberculoma presenting as pituitary apoplexy. Neurol India 2001;49(4):407–410. 22. Sharma MC, Vaish S, Arora R, et al. Composite pituitary adenoma and intrasellar tuberculoma: report of a rare case. Pathol Oncol Res 2001;7(1):74–76. 23. Stalldecker G, Diez S, Carabelli A, et al. Pituitary stalk tuberculoma. Pituitary 2002;5:155–162.

24. Paramo C, de la Fuente J, Nodar A, et al. Intrasellar tuberculoma—a difficult diagnosis. Infection 2002; 30(1):35–37. 25. Domingues FS, de Souza JM, Chagas H, et al. Pituitary tuberculoma: an unusual lesion of sellar region. Pituitary 2002;5(3):149–153. 26. Satyarthee GD, Mahapatra AK. Diabetes insipidus in sellar-suprasellar tuberculoma. J Clin Neurosci 2003; 10(4):497–499. 27. Singh S. Pituitary tuberculoma: magnetic resonance imaging. Neurol India 2003;51(4):548–550. 28. Andronikou S, Furlan G, Fieggen AG, et al. Two unusual causes of pituitary stalk thickening in children without clinical features of diabetes insipidus. Pediatr Radiol 2003;33(7):499–502. 29. Desai KI, Nadkarni TD, Goel A. Tuberculomas of hypophysitis cerebri: A report of five cases. J Clin Neurosci 2003;10:562–566. 30. Deogaonkar M, De R, Sil K, Das S. Pituitary tuberculosis presenting as pituitary apoplexy. Int J Infect Dis 2006;10(4):338–339. 31. Klassen KP, Curtis GM, Ohio C. Tuberculous abscess of the thyroid gland. Surgery 1945;17:552–559. 32. Bulbuloglu E, Ciralik H, Okur E, et al. Tuberculosis of the thyroid gland: review of the literature. World J Surg 2006;30:149–155. 33. Al-Mulhim AA, Zakaria HM, Hadi MSAA, et al. Thyroid tuberculosis mimicking carcinoma: report of two cases. Surgery Today 2002;32:1064–1067. 34. Simkus PE. Thyroid tuberculosis Medicina 2004; 40:201–204. 35. Unnikrishnan AG, Koshy GR, Rajaratnam S, et al. Suppurative neck abscess due to tuberculous thyroiditis. J Assoc Physicians India 2002;50:610–611. 36. El Malki HO, El Absi M, Mohsine R, et al. La tuberculose de la thyroide. Diagnostic et traitment. Ann Chir 2002;127:385–387. 37. Mondal A, Patra DK. Efficacy of fine needle aspiration cytology in the diagnosis of tuberculosis of the thyroid gland: a study of 18 cases. J Laryngol Otol 1995;109:36–38. 38. Jakob PM, Sukumar GC, Nair A, et al. Parathyroid adenoma with necrotizing granulomatous inflammation presenting as primary hyperparathyroidism. Endocr Pathol 2005;16(2): 157–160. 39. Kar DK, Agarwal G, Metha B, et al. Tuberculous granulomatous inflammation associated with adenoma of parathyroid gland manifesting as primary hyperparathyroidism. Endocr Pathol 2001;12(3): 355–359. 40. Wolfgang O. Adrenal insufficiency. N Engl J Med 1996;335:1206–1212. 41. Willis AC, Vince FP. The prevalence of Addison’s disease in Coventry, UK. Postgrad Med J 1997; 73(859):286–288. 42. Kong MF, Jeffcoate W. Eighty-six cases of Addison’s disease. Clin Endocrinol 1994;41(6):757–761. 43. Wilms GE, Baert AL, Kint EJ, et al. Computed tomographic findings in bilateral adrenal tuberculosis. Radiology 1983;146:729–730. 44. Betterle C, Dal Pra C, Mantero F, et al. Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction. Endocr Rev 2002;23:327–364. 45. Benini F, Savarin T, Senna GE, et al. Diagnostic and therapeutic problems in a case of adrenal tuberculosis and acute Addison’s disease. J Endocrinol Invest 1990;13(7):597–600.

46. Serter R, Koc G, Demirbas B, et al. Acute adrenal crisis together with unilateral adrenal mass caused by isolated tuberculosis of adrenal gland. Endocr Pract 2003;9(2):157–161. 47. Guttman PH. Addison’s disease: a statistical analysis of 566 cases and a study of the pathology. Arch Pathol 1930;10:742–785. 48. Vita JA, Silverberg SJ, Goland RS, et al. Clinical clues to the cause of Addison’s disease. Am J Med 1985; 78(3):461–466. 49. Liatsikos EN, Kalogeropoulou CP, Papathanassiou Z, et al. Primary adrenal tuberculosis: role of computed tomography and CT-guided biopsy in diagnosis. Urol Int 2006;76(3):285–287. 50. Llewelyn M, Adler M, Steer K, et al. Acute adrenal insufficiency precipitated by isolated involvement of the adrenal gland by tuberculosis. J Infect 1999; 39(3):244–245. 51. Efremidis SC, Harsoulis F, Douma S, et al. Adrenal insufficiency with enlarged adrenals. Abdom Imaging 1996;21(2):168–171. 52. Hawken MP, Ojoo JC, Morris JS, et al. No increased prevalence of adrenocortical insufficiency in human immunodeficiency virus-associated tuberculosis. Tuber Lung Dis 1996;77(5):444–448. 53. Kelestimur E. The endocrinology of adrenal tuberculosis: the effects of tuberculosis on the hypothalamo-pituitary-adrenal axis and adrenocortical function. J Endocrinol Invest 2004;27(4):380–386. 54. Alkhuja S, Miller A. Tuberculosis and sudden death: a case report and review. Heart Lung 2001; 30(5):388–391. 55. Kwon HS, Kim SI, Yoo SJ, et al. Adrenal tuberculosis in Cushing’s disease with bilateral macronodular adrenocortical hyperplasia. Endocr J 2006;53(2):219–223. 56. May ME, Vaughn ED, Carey RM. Adrenocortical insufficiency-clinical aspects. In: Vaughan ED Jr, Carey RM (eds). Adrenal Disorders. New York: Thieme, 1989: 171–189. 57. Bhatia E, Jain SK, Gupta RK, et al. Tuberculous Addison’s disease: lack of normalization of adrenocortical function after anti-tuberculous chemotherapy. Clin Endocrinol (Oxf) 1998; 48(3):355–359. 58. Demir K, Kaymakoglu S, Besisik F, et al. Solitary pancreatic tuberculosis in immunocompetent patients mimicking pancreatic carcinoma. J Gastroenterol Hepatol 2001;16:1071–1074. 59. Jaber B, Gleckman R. Tuberculous pancreatic abscess as an initial AIDS-defining disorder in a patient infected with the human immunodeficiency virus: case report and review. Clin Infect Dis 1995;20:890–894. 60. Coelho JC, Wiederkehr JC, Parolin MB, et al. Isolated tuberculosis of the pancreas after orthotopic liver transplantation. Liver Transpl Surg 1999;5:153–155. 61. Schneider A, von Birgelen C, Duhrsen U, et al. Two cases of pancreatic tuberculosis in nonimmunocompromised patients. A diagnostic challenge and a rare cause of portal hypertension. Pancreatology 2002;2:69–73. 62. Woodfield JC, Windsor JA, Godfrey CC, et al. Diagnosis and management of isolated pancreatic tuberculosis: recent experience and literature review. ANZ J Surg 2004;74:368–371. 63. Knowles KF, Saltman D, Robson HG, et al. Tuberculous pancreatitis. Tubercle 1990;71:65–68. 64. Ahlawat SK, Charabaty-Pishvaian A, Lewis JH, et al. Pancreatic tuberculosis diagnosed with endoscopic ultrasound guided fine needle aspiration. JOP 2005;10;6(6):598–602.

513

SECTION

5

CLINICAL PRESENTATIONS OF TUBERCULOSIS

65. Chaudhary A, Negi SS, Sachdev AK, et al. Pancreatic tuberculosis: still a histopathological diagnosis. Dig Surg 2002;19(5):389–392. 66. Evans JD, Hamanaka Y, Olliff SP, et al. Tuberculosis of the pancreas presenting as metastatic pancreatic carcinoma. A case report and review of the literature. Dig Surg 2000;17(2):183–187. 67. Small G, Wilks D. Pancreatic mass caused by Mycobacterium tuberculosis with reduced drug sensitivity. J Infect 2001;42:201–202. 68. Karia K, Mathur SK. Tuberculous cold abscess simulating pancreatic pseudocyst. J Postgrad Med 2000;46:33–34. 69. Stock KP, Riemann JF, Stadler W, et al. Tuberculosis of the pancreas. Endoscopy 1981;13:178–180. 70. Franco-Paredes C, Leonard M, Jurado R, et al. Tuberculosis of the pancreas: report of two cases and review of the literature. Am J Med Sci 2002;323:54–58. 71. Liu Q, He Z, Bie P. Solitary pancreatic tuberculous abscess mimicking pancreatic cystadenocarcinoma: A case report. BMC Gastrenterol 2003;3:1.

514

72. Bornman PC, Beckingham IJ. ABC of diseases of liver, pancreas, and biliary system: Pancreatic tumours. BMJ 2001;322:721–723. 73. Martin I, Hammond P, Scott J, et al. Cystic tumours of the pancreas. Br J Surg 1998;85:1484–1486. 74. D’Cruz S, Sachdev A, Kaur L, et al. Fine needle aspiration diagnosis of isolated pancreatic tuberculosis. A case report and review of literature. JOP 2003; 4(4):158–162. 75. Hulnick DH, Megibow AJ, Naidich DP, et al. Abdominal tuberculosis: CT evaluation. Radiology 1985;157:199–204. 76. De Backer AI, Mortele KJ, Bomans P, et al. Tuberculosis of the pancreas: MRI features. AJR Am J Roentgenol 2005;184(1):50–54. 77. Garbyal RS, Gupta P, Kumar S, Anshu. Diagnosis of isolated tuberculous orchitis by fine-needle aspiration cytology. Diagn Cytopathol 2006;34(10):698–700. 78. Goodman P, Maklad NF, Verani RR, et al. Tuberculous abscess of the testicle in AIDS: sonographic demonstration. Urol Radiol 1990;12(1):53–55.

79. Kumar PV, Owji SM, Khezri AA. Tuberculous orchitis diagnosed by fine needle aspiration cytology. Acta Cytol 1996;40(6):1253–1256. 80. Gemmel C, Jacek G, Lucking HC, et al. [Scrotal abscess with inguinal lymph node swelling in an 86-year-old man.] Dtsch Med Wochenschr 2004; 129(39):2032–2034. [In German.] 81. Muttarak M, Peh WC. Case 91: Tuberculous epididymo-orchitis. Radiology 2006;238(2):748–751. 82. Debnath PR, Tripathi R, Agarwal LD, et al. Tuberculosis in transverse testicular ectopic testis, a diagnostic dilemma: case report. Indian J Tuberc 2006;53:27–29. 83. Steller J. [Ovarian tuberculosis.] Gynakol Geburtshilfliche Rundsch 2001;41(4):236–239. [In German.] 84. Parikh FR, Nadkarni SG, Kamat SA, et al. Genital tuberculosis—a major pelvic factor causing infertility in Indian women. Fertil Steril 1997; 67(3):497–500.