K.E.M.
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Case of the Month
Case of the Month
Darling’s disease
Darling’s disease
Contributed by : Milan Talati
Contributed by : Milan Talati
In 1905, Samuel Taylor Darling a world-leading pathologist discovered Histoplasmosis to be a fungal infection. Darling studied smears and slides made from tissues of a carpenter with an unknown infection and observed defense cells that resembled Plasmodium organisms.
Introduction :
Introduction :
Histoplasmosis, also known as Darling’s disease is a form of endemic mycosis from Ohio or Mississippi river valleys caused by H. capsulatum. It grows in the soil, which is heavily contaminated with bird droppings. The inhaled spores are engulfed by macrophages which develop into intracellular yeast forms. The organism disseminates throughout the body, especially the liver and spleen. The granulomatous foci heal with calcification. While most cases remain asymptomatic, it may go on to develop pneumonia and cavitatory lung disease. In rare cases it invades the adrenal gland and leads to adrenal insufficiency.
Histoplasmosis, also known as Darling’s disease is a form of endemic mycosis from Ohio or Mississippi river valleys caused by H. capsulatum. It grows in the soil, which is heavily contaminated with bird droppings. The inhaled spores are engulfed by macrophages which develop into intracellular yeast forms. The organism disseminates throughout the body, especially the liver and spleen. The granulomatous foci heal with calcification. While most cases remain asymptomatic, it may go on to develop pneumonia and cavitatory lung disease. In rare cases it invades the adrenal gland and leads to adrenal insufficiency.
Clinical Profile:
Clinical Profile:
A 55 year old man presented with breathlessness, cough, weight loss since one month; worsening lethargy and weakness since two weeks.
A 55 year old man presented with breathlessness, cough, weight loss since one month; worsening lethargy and weakness since two weeks.
The patient is known to have diabetes since two years.
The patient is known to have diabetes since two years.
Biochemical investigations:
Biochemical investigations:
Serum aldosterone: 3.5ng/100ml
Serum aldosterone: 3.5ng/100ml
Serum cortisol: 2.5mcg/dl
Serum cortisol: 2.5mcg/dl
Radiological findings
Radiological findings
Frontal chest radiograph: There is a well-defined soft tissue opacity involving middle zone of the right lung with spiculated margins and no calcific foci.
Frontal chest radiograph: There is a well-defined soft tissue opacity involving middle zone of the right lung with spiculated margins and no calcific foci.
NCCT brain: There are multilobulated isodense nodules involving the skin.
NCCT brain: There are multilobulated isodense nodules involving the skin.
HRCT Chest: There are multiple. well-defined areas of cavitating consolidations with spiculated margins. There are multiple enlarged mediastinal lymph nodes with faint calcification.
HRCT Chest: There are multiple. well-defined areas of cavitating consolidations with spiculated margins. There are multiple enlarged mediastinal lymph nodes with faint calcification.
CECT Abdomen: Both adrenals are bulky and have hypo to isodense lobulated appearance. There are foci of calcification. The adrenals are non-enhancing on successive arterial and venous phases.
CECT Abdomen: Both adrenals are bulky and have hypo to isodense lobulated appearance. There are foci of calcification. The adrenals are non-enhancing on successive arterial and venous phases.
MRI Abdomen:There is thickening of both adrenals with mild hyperintensity on T2 WI. The adrenals show restriction on diffusion weighted imaging with drop on ADC. The in and opposed T1 phase show no drop in signal intensity on opposed phase suggestive of absence of microscopic fat within the adrenals.
MRI Abdomen:There is thickening of both adrenals with mild hyperintensity on T2 WI. The adrenals show restriction on diffusion weighted imaging with drop on ADC. The in and opposed T1 phase show no drop in signal intensity on opposed phase suggestive of absence of microscopic fat within the adrenals.
FIG 1 The frontal chest radiograph shows a well-defined soft tissue opacity involving middle zone of the right lung with spiculated margins and no calcific foci. There is left sided moderate pleural effusion.
FIG 2A NCCT head shows multilobulated isodense nodules involving the skin.
FIG 2 B, C: HRCT Chest: There are multiple well-defined areas of cavitating consolidations with spiculated margins. There are multiple enlarged mediastinal lymph nodes with soft calcification,.
FIG 3 A B C D: CECT abdomen- Both adrenals are bulky and have hypo to isodense lobulated appearance. There are calcifications in the adrenals. Arterial and venous phase shows non enhancing enlarged adrenals.
FIG 4 A B C D E: T2W Axial MRI shows thickening of both adrenals with mild hyperintensity. There are areas of diffusion restriction with signal drop in ADC map. The in and opposed T1 phase shows no drop in signal intensity on opposed phase suggestive of absence of microscopic fat within the adrenals.
Radiological diagnosis:
Radiological diagnosis:
• Tuberculosis
• Tuberculosis
• Histoplasmosis
• Histoplasmosis
Pathological diagnosis
Pathological diagnosis
CT guided biopsy of the adrenal mass followed by microbiological examination of the lesion was done which revealed histoplasmosis.
CT guided biopsy of the adrenal mass followed by microbiological examination of the lesion was done which revealed histoplasmosis.
Final diagnosis:
Final diagnosis:
Disseminated histoplasmosis with adrenal insufficiency
Disseminated histoplasmosis with adrenal insufficiency
Management:
Management:
Antifungal medications were started .
Antifungal medications were started .
Mineralocorticoids were also added to the regimen to tackle the adrenal insufficiency.
Mineralocorticoids were also added to the regimen to tackle the adrenal insufficiency.
Timeline:
Timeline:
Discussion
Discussion
Histoplasmosis also known as Darling’s disease is a form of endemic mycosis from Ohio or Mississippi river valleys caused by H. capsulatum. It is a dimorphic fungus which exists in its yeast form at 37 degrees C and in mold form at 20 degrees C.. It grows in the soil, which is heavily contaminated with bird droppings. (1)
Histoplasmosis also known as Darling’s disease is a form of endemic mycosis from Ohio or Mississippi river valleys caused by H. capsulatum. It is a dimorphic fungus which exists in its yeast form at 37 degrees C and in mold form at 20 degrees C.. It grows in the soil, which is heavily contaminated with bird droppings. (1)
The inhaled spores are engulfed by macrophages which develop into intracellular yeast forms. The organism disseminates throughout the body, especially to the liver and spleen. The granulomatous foci heal with calcification. While most cases remain asymptomatic, it may go on to develop pneumonia and cavitatory lung disease. In rare cases it invades the adrenal gland and leads to adrenal insufficiency and electrolyte imbalance. It is diagnosed by imaging and lab diagnosis using SDA cultures, Microscopy, ELISA or PCR.
The inhaled spores are engulfed by macrophages which develop into intracellular yeast forms. The organism disseminates throughout the body, especially to the liver and spleen. The granulomatous foci heal with calcification. While most cases remain asymptomatic, it may go on to develop pneumonia and cavitatory lung disease. In rare cases it invades the adrenal gland and leads to adrenal insufficiency and electrolyte imbalance. It is diagnosed by imaging and lab diagnosis using SDA cultures, Microscopy, ELISA or PCR.
Adrenal histoplasmosis is a rare complication of the disseminated disease.
Adrenal histoplasmosis is a rare complication of the disseminated disease.
Normally the adrenals are of the thickness which is equal to that of the crus of diaphragm.
Normally the adrenals are of the thickness which is equal to that of the crus of diaphragm.
Any thickness greater than that of the crus is pathological and needs further evaluation to reach the diagnosis. (2,3)
Any thickness greater than that of the crus is pathological and needs further evaluation to reach the diagnosis. (2,3)
The differential diagnosis of the adrenal enlargement with their respective findings includes-
The differential diagnosis of the adrenal enlargement with their respective findings includes-
• Primary pigmented nodular adrenal dysplasia- the adrenal glands are not significantly enlarged, but contain multiple bilateral nodules, typically 2-5 mm in diameter, although in older patients they may be as large as 1-2 cm. The intervening gland appears atrophic.(4)
• Primary pigmented nodular adrenal dysplasia- the adrenal glands are not significantly enlarged, but contain multiple bilateral nodules, typically 2-5 mm in diameter, although in older patients they may be as large as 1-2 cm. The intervening gland appears atrophic.(4)
• Macronodular adrenal hyperplasia, which refers to a morphological type of adrenal hyperplasia in which there is adrenal enlargement in the form of large distinct nodules. It can be congenital or acquired. (5,6)
• Macronodular adrenal hyperplasia, which refers to a morphological type of adrenal hyperplasia in which there is adrenal enlargement in the form of large distinct nodules. It can be congenital or acquired. (5,6)
• Adrenal metastases can have variable CT appearances. They are known to show venous washout.
• Adrenal metastases can have variable CT appearances. They are known to show venous washout.
• Adrenal hematomas characteristically appears round or oval, often with surrounding periadrenal fat stranding.
• Adrenal hematomas characteristically appears round or oval, often with surrounding periadrenal fat stranding.
Adrenal hematomas decrease in size and attenuation over time, and most resolve completely.
Adrenal hematomas decrease in size and attenuation over time, and most resolve completely.
• Adrenal lymphoma maybe seen as bulky adrenal masses. Usually of soft tissue attenuation (40-60 HU) with mild progressive enhancement after contrast medium administration.
• Adrenal lymphoma maybe seen as bulky adrenal masses. Usually of soft tissue attenuation (40-60 HU) with mild progressive enhancement after contrast medium administration.
• Adrenal pheochromocytoma are usually unilateral and shows avid arterial enhancement with areas of necrosis and cysts.(7)
• Adrenal pheochromocytoma are usually unilateral and shows avid arterial enhancement with areas of necrosis and cysts.(7)
Adrenal histoplasmosis is a rare complication of the disseminated disease.(8)
Adrenal histoplasmosis is a rare complication of the disseminated disease.(8)
Precise knowledge about the radiological and clinical manifestations aid in diagnosis and prompt treatment. Diagnosis and differentiation of the two close mimics (tuberculosis and histoplasmosis) and other granulomatous diseases involving both the adrenals is vital for effective management of the resultant glucocorticoid deficiency. Parenteral itraconazole or Amphotericin B with external glucocorticoid supplementation is the treatment of choice when fungal etiology is confirmed.
Precise knowledge about the radiological and clinical manifestations aid in diagnosis and prompt treatment. Diagnosis and differentiation of the two close mimics (tuberculosis and histoplasmosis) and other granulomatous diseases involving both the adrenals is vital for effective management of the resultant glucocorticoid deficiency. Parenteral itraconazole or Amphotericin B with external glucocorticoid supplementation is the treatment of choice when fungal etiology is confirmed.
References:
References:
1. Warren’s Levinson review of medical microbiology and immunology.
1. Warren’s Levinson review of medical microbiology and immunology.
2. D A Wilson, H G Muchmore, R G Tisdal, A Fahmy, J V Pitha. Histoplasmosis of the adrenal glands studied by CT. (1984) Radiology. 150 (3): 779-83.
2. D A Wilson, H G Muchmore, R G Tisdal, A Fahmy, J V Pitha. Histoplasmosis of the adrenal glands studied by CT. (1984) Radiology. 150 (3): 779-83.
3. Mukherjee, Jagat J., Villa, Michael L., Tan, Lenny, Lee, K. O.. Bilateral Adrenal Masses Due to Histoplasmosis. (2005) The Journal of Clinical Endocrinology & Metabolism. 90 (12): 6725.
3. Mukherjee, Jagat J., Villa, Michael L., Tan, Lenny, Lee, K. O.. Bilateral Adrenal Masses Due to Histoplasmosis. (2005) The Journal of Clinical Endocrinology & Metabolism. 90 (12): 6725.
4. Rockall AG, Babar SA, Sohaib SA et-al. CT and MR imaging of the adrenal glands in ACTH-independent cushing syndrome. Radiographics. 24 (2): 435-52.
4. Rockall AG, Babar SA, Sohaib SA et-al. CT and MR imaging of the adrenal glands in ACTH-independent cushing syndrome. Radiographics. 24 (2): 435-52.
5. Doppman JL, Chrousos GP, Papanicolaou DA et-al. Adrenocorticotropin-independent macronodular adrenal hyperplasia: an uncommon cause of primary adrenal hypercortisolism. Radiology. 2000;216 (3): 797-802.
5. Doppman JL, Chrousos GP, Papanicolaou DA et-al. Adrenocorticotropin-independent macronodular adrenal hyperplasia: an uncommon cause of primary adrenal hypercortisolism. Radiology. 2000;216 (3): 797-802.
6. Doppman JL, Nieman LK, Travis WD et-al. CT and MR imaging of massive macronodular adrenocortical disease: a rare cause of autonomous primary adrenal hypercortisolism. J Comput Assist Tomogr. 15 (5): 773-9.
6. Doppman JL, Nieman LK, Travis WD et-al. CT and MR imaging of massive macronodular adrenocortical disease: a rare cause of autonomous primary adrenal hypercortisolism. J Comput Assist Tomogr. 15 (5): 773-9.
7. Townsend RR, McGinnis PA, Tuan WM, Thrasher K. Case report: bilateral adrenal pheochromocytoma. (1994) The American journal of the medical sciences. 308 (2): 123-5.
7. Townsend RR, McGinnis PA, Tuan WM, Thrasher K. Case report: bilateral adrenal pheochromocytoma. (1994) The American journal of the medical sciences. 308 (2): 123-5.
8. D A Wilson, H G Muchmore, R G Tisdal, A Fahmy, J V Pitha. Histoplasmosis of the adrenal glands studied by CT. (1984) Radiology. 150 (3): 779-83.
8. D A Wilson, H G Muchmore, R G Tisdal, A Fahmy, J V Pitha. Histoplasmosis of the adrenal glands studied by CT. (1984) Radiology. 150 (3): 779-83.