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PRKAR1A-negative familial Cushing's syndrome: two case reports.

Lim LL, Kitan N, Paramasivam SS, Ratnasingam J, Ibrahim L, Chan SP, Tan AT, Vethakkan SR - J Med Case Rep (2015)

Bottom Line: Completion of contralateral adrenalectomy was performed upon recognition of typical histologic characteristics of primary pigmented nodular adrenocortical disease found in an initial left adrenalectomy specimen.He was successfully treated with bilateral adrenalectomy.Long-term surveillance is imperative in patients with confirmed Carney's complex and in those who have not undergone complete genetic testing to exclude this hereditary disorder.

View Article: PubMed Central - PubMed

Affiliation: Division of Endocrinology, Department of Internal Medicine, University of Malaya Medical Center, Lembah Pantai, 59100, Kuala Lumpur, Malaysia. leelinglimll@gmail.com.

ABSTRACT

Introduction: Determining the etiology of Cushing's syndrome is very challenging to endocrinologists, with most of the difficulty arising from subtype differentiation of adrenocorticotropic hormone-dependent Cushing's syndrome. We present the pitfalls of evaluating a rare cause of adrenocorticotropic hormone-independent Cushing's syndrome in the transition period between adolescence and adulthood.

Case presentation: A sibling pair with familial isolated primary pigmented nodular adrenocortical disease is described. The index case, a 20-year-old Chinese woman, presented with premenopausal osteoporosis with T12 compression fracture and young hypertension. Biochemical analysis confirmed adrenocorticotropic hormone-independent Cushing's syndrome (elevated 0800 h plasma cortisol 808 nmol/L with suppressed adrenocorticotropic hormone level <5 pg/ml). Computed tomography of her adrenal glands revealed a 0.7-cm left adrenal hypodense nodule. After a left adrenalectomy, she had residual hypercortisolism (progressive weight gain, new T10 compression fracture, and not glucocorticoid-dependent postoperatively). Completion of contralateral adrenalectomy was performed upon recognition of typical histologic characteristics of primary pigmented nodular adrenocortical disease found in an initial left adrenalectomy specimen. Similarly, her younger brother developed adrenocorticotropic hormone-independent Cushing's syndrome at age 18 years, with typical cushingoid habitus, but no osteoporosis or hypertension. His adrenal computed tomographic scans showed micronodularities over bilateral adrenal glands. He was successfully treated with bilateral adrenalectomy. Screening for Carney's complex and PRKAR1A gene mutation was negative. Signs and symptoms of Cushing's syndrome resolved after bilateral adrenalectomy for both patients. They were placed on lifelong glucocorticoid and mineralocorticoid replacement therapy and long-term surveillance for Carney's complex.

Conclusions: The cases of these two patients illustrate the difficulties involved in diagnosing primary pigmented nodular adrenocortical disease, a variant of adrenocorticotropic hormone-independent Cushing's syndrome that is managed with bilateral adrenalectomy. A high index of suspicion for this disease is needed, especially in adolescents with adrenocorticotropic hormone-independent Cushing's syndrome who have a significant family history, features of Carney's complex, and no resolution of Cushing's syndrome after unilateral adrenalectomy. Patients with primary pigmented nodular adrenocortical disease can either have bilateral/multiple adrenal nodules or normal adrenal glands visualized by computed tomography. Long-term surveillance is imperative in patients with confirmed Carney's complex and in those who have not undergone complete genetic testing to exclude this hereditary disorder.

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Computed tomography of the adrenal glands and gross pathology of the lesions. Patient 1: Computed tomographic scan of her adrenal glands shows a nodular left adrenal gland with hypodense lesions (red arrow) and a normal right adrenal gland (a), and histologic specimen shows cut surface of left adrenal gland with multiple brown nodules (c). Patient 2: Computed tomographic scan shows a hypodense micronodular appearance of both adrenal glands (red arrows) (b), and gross histologic specimens reveal adrenal hyperplasia with multiple pale brown nodules (d)
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Fig1: Computed tomography of the adrenal glands and gross pathology of the lesions. Patient 1: Computed tomographic scan of her adrenal glands shows a nodular left adrenal gland with hypodense lesions (red arrow) and a normal right adrenal gland (a), and histologic specimen shows cut surface of left adrenal gland with multiple brown nodules (c). Patient 2: Computed tomographic scan shows a hypodense micronodular appearance of both adrenal glands (red arrows) (b), and gross histologic specimens reveal adrenal hyperplasia with multiple pale brown nodules (d)

Mentions: Her blood test results excluded diabetes mellitus and electrolyte abnormalities. Her hormone tests revealed hypercortisolemia (0800 h plasma cortisol 808 nmol/L), and a suppressed ACTH level <5 pg/ml. Her total serum testosterone was mildly elevated (Table 1). ACTH-independent CS was confirmed after a 48-h, 2-mg, low-dose dexamethasone suppression test (LDDST) failed to suppress endogenous cortisol secretion (0800 h post-LDDST plasma cortisol 621 nmol/L). A 0.7-cm left adrenal hypodense nodule was identified by performing adrenal computed tomography (CT) and was reported as an adenoma (Fig. 1a). An x-ray of her thoracolumbar spine disclosed a T12 compression fracture. Dual-energy bone densitometry (DXA) revealed low bone mineral density (BMD) with Z-scores of −4.5 (L1-L2) and −3.2 (femoral neck).Table 1


PRKAR1A-negative familial Cushing's syndrome: two case reports.

Lim LL, Kitan N, Paramasivam SS, Ratnasingam J, Ibrahim L, Chan SP, Tan AT, Vethakkan SR - J Med Case Rep (2015)

Computed tomography of the adrenal glands and gross pathology of the lesions. Patient 1: Computed tomographic scan of her adrenal glands shows a nodular left adrenal gland with hypodense lesions (red arrow) and a normal right adrenal gland (a), and histologic specimen shows cut surface of left adrenal gland with multiple brown nodules (c). Patient 2: Computed tomographic scan shows a hypodense micronodular appearance of both adrenal glands (red arrows) (b), and gross histologic specimens reveal adrenal hyperplasia with multiple pale brown nodules (d)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4666013&req=5

Fig1: Computed tomography of the adrenal glands and gross pathology of the lesions. Patient 1: Computed tomographic scan of her adrenal glands shows a nodular left adrenal gland with hypodense lesions (red arrow) and a normal right adrenal gland (a), and histologic specimen shows cut surface of left adrenal gland with multiple brown nodules (c). Patient 2: Computed tomographic scan shows a hypodense micronodular appearance of both adrenal glands (red arrows) (b), and gross histologic specimens reveal adrenal hyperplasia with multiple pale brown nodules (d)
Mentions: Her blood test results excluded diabetes mellitus and electrolyte abnormalities. Her hormone tests revealed hypercortisolemia (0800 h plasma cortisol 808 nmol/L), and a suppressed ACTH level <5 pg/ml. Her total serum testosterone was mildly elevated (Table 1). ACTH-independent CS was confirmed after a 48-h, 2-mg, low-dose dexamethasone suppression test (LDDST) failed to suppress endogenous cortisol secretion (0800 h post-LDDST plasma cortisol 621 nmol/L). A 0.7-cm left adrenal hypodense nodule was identified by performing adrenal computed tomography (CT) and was reported as an adenoma (Fig. 1a). An x-ray of her thoracolumbar spine disclosed a T12 compression fracture. Dual-energy bone densitometry (DXA) revealed low bone mineral density (BMD) with Z-scores of −4.5 (L1-L2) and −3.2 (femoral neck).Table 1

Bottom Line: Completion of contralateral adrenalectomy was performed upon recognition of typical histologic characteristics of primary pigmented nodular adrenocortical disease found in an initial left adrenalectomy specimen.He was successfully treated with bilateral adrenalectomy.Long-term surveillance is imperative in patients with confirmed Carney's complex and in those who have not undergone complete genetic testing to exclude this hereditary disorder.

View Article: PubMed Central - PubMed

Affiliation: Division of Endocrinology, Department of Internal Medicine, University of Malaya Medical Center, Lembah Pantai, 59100, Kuala Lumpur, Malaysia. leelinglimll@gmail.com.

ABSTRACT

Introduction: Determining the etiology of Cushing's syndrome is very challenging to endocrinologists, with most of the difficulty arising from subtype differentiation of adrenocorticotropic hormone-dependent Cushing's syndrome. We present the pitfalls of evaluating a rare cause of adrenocorticotropic hormone-independent Cushing's syndrome in the transition period between adolescence and adulthood.

Case presentation: A sibling pair with familial isolated primary pigmented nodular adrenocortical disease is described. The index case, a 20-year-old Chinese woman, presented with premenopausal osteoporosis with T12 compression fracture and young hypertension. Biochemical analysis confirmed adrenocorticotropic hormone-independent Cushing's syndrome (elevated 0800 h plasma cortisol 808 nmol/L with suppressed adrenocorticotropic hormone level <5 pg/ml). Computed tomography of her adrenal glands revealed a 0.7-cm left adrenal hypodense nodule. After a left adrenalectomy, she had residual hypercortisolism (progressive weight gain, new T10 compression fracture, and not glucocorticoid-dependent postoperatively). Completion of contralateral adrenalectomy was performed upon recognition of typical histologic characteristics of primary pigmented nodular adrenocortical disease found in an initial left adrenalectomy specimen. Similarly, her younger brother developed adrenocorticotropic hormone-independent Cushing's syndrome at age 18 years, with typical cushingoid habitus, but no osteoporosis or hypertension. His adrenal computed tomographic scans showed micronodularities over bilateral adrenal glands. He was successfully treated with bilateral adrenalectomy. Screening for Carney's complex and PRKAR1A gene mutation was negative. Signs and symptoms of Cushing's syndrome resolved after bilateral adrenalectomy for both patients. They were placed on lifelong glucocorticoid and mineralocorticoid replacement therapy and long-term surveillance for Carney's complex.

Conclusions: The cases of these two patients illustrate the difficulties involved in diagnosing primary pigmented nodular adrenocortical disease, a variant of adrenocorticotropic hormone-independent Cushing's syndrome that is managed with bilateral adrenalectomy. A high index of suspicion for this disease is needed, especially in adolescents with adrenocorticotropic hormone-independent Cushing's syndrome who have a significant family history, features of Carney's complex, and no resolution of Cushing's syndrome after unilateral adrenalectomy. Patients with primary pigmented nodular adrenocortical disease can either have bilateral/multiple adrenal nodules or normal adrenal glands visualized by computed tomography. Long-term surveillance is imperative in patients with confirmed Carney's complex and in those who have not undergone complete genetic testing to exclude this hereditary disorder.

Show MeSH
Related in: MedlinePlus