Cushing’s syndrome due to primary pigmented nodular adrenal disease in two brothers with Carney complex

Object. The authors present their neurosurgical experience with Carney complex. Carney complex, characterized by spotty skin pigmentation, cardiac myxomas, primary pigmented nodular adrenocortical disease, pituitary tumors, and nerve sheath tumors (NSTs), is a recently described, rare, autosomal-dominant familial syndrome that is relatively unknown to neurosurgeons. Neurosurgery is required to treat pituitary adenomas and a rare NST, the psammomatous melanotic schwannoma (PMS), in patients with Carney complex. Cushing's syndrome, a common component of the complex, is caused by primary pigmented nodular adrenocortical disease and is not secondary to an adrenocorticotropic hormone-secreting pituitary adenoma.Methods. The authors reviewed 14 cases of Carney complex, five from the literature and nine from their own experience. Of the 14 pituitary adenomas recognized in association with Carney complex, 12 developed growth hormone (GH) hypersecretion (producing gigantism in two patients and acromegaly in 10), and results of immunohistochemical studies in one of the other two were positive for GH. The association of PMSs with Carney complex was established in 1990. Of the reported tumors, 28% were associated with spinal nerve sheaths. The spinal tumors occurred in adults (mean age 32 years, range 18–49 years) who presented with pain and radiculopathy. These NSTs may be malignant (10%) and, as with the cardiac myxomas, are associated with significant rates of morbidity and mortality.Conclusions. Because of the surgical comorbidity associated with cardiac myxoma and/or Cushing's syndrome, recognition of Carney complex has important implications for perisurgical patient management and family screening. Study of the genetics of Carney complex and of the biological abnormalities associated with the tumors may provide insight into the general pathobiological abnormalities associated with the tumors may provide insight into the general pathobiological features of pituitary adenomas and NSTs.

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3. The Handling of Adrenal Disease and Problems, 1) Adrenal Incidentaloma and Subclinical Cushing's Syndrome

Nihon Naika Gakkai Zasshi ◽

10.2169/naika.101.941 ◽

2012 ◽

Vol 101 (4) ◽

pp. 941-948 ◽

Cited By ~ 1

Author(s):

Ryoichi Takayanagi ◽

Hisaya Kawate ◽

Toshihiko Yanase

Keyword(s):

Cushing’S Syndrome ◽

Adrenal Incidentaloma ◽

Cushing's Syndrome ◽

Subclinical Cushing’S Syndrome ◽

Adrenal Disease

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ACTH-independent massive bilateral adrenal disease (AIMBAD): A subtype of Cushing's syndrome with major diagnostic and therapeutic implications

Acta Endocrinologica ◽

10.1530/eje.0.1310067 ◽

1994 ◽

Vol 131 (1) ◽

pp. 67-73 ◽

Cited By ~ 55

Author(s):

Steven A Lieberman ◽

T Ross Eccleshall ◽

David Feldman

Keyword(s):

Cushing’S Syndrome ◽

Adrenal Glands ◽

Medical Center ◽

Serum Cortisol ◽

Cushing's Syndrome ◽

Bilateral Adrenalectomy ◽

Preoperative Treatment ◽

Therapeutic Implications ◽

Adrenal Imaging ◽

Adrenal Disease

Lieberman SA, Eccleshall TR, Feldman D. ACTH-independent massive bilateral adrenal disease (AIMBAD): a subtype of Cushing's syndrome with major diagnostic and therapeutic implications. Eur J Endocrinol 1994:131:67–73. ISSN 0804–4643 A 49-year-old man with classic manifestations of Cushing's syndrome had undetectable levels of ACTH, lack of suppression of hypercortisolism with dexamethasone in doses of 2, 8, or 16 mg per day, bilaterally enlarged adrenal glands on MRI, and bilateral adrenal uptake of iodocholesterol. Preoperative treatment with ketoconazole lowered blood pressure and serum cortisol and produced symptoms of steroid withdrawal. Bilateral adrenalectomy revealed massively enlarged adrenal glands (left: 199 g, right: 93 g). Sequencing of the gene encoding the stimulatory G protein, Gsα, did not show either of two activating mutations previously reported in patients with McCune–Albright syndrome or acromegaly. Twenty-three previous cases of Cushing's syndrome due to ACTH-independent massive bilateral adrenal disease (AIMBAD) have been reported. AIMBAD may cause confusion in the differential diagnosis of Cushing's syndrome as endocrine testing suggests a unilateral, ACTHindependent process while adrenal imaging demonstrates bilateral abnormalities. Bilateral adrenalectomy is curative and appears to carry little risk of Nelson's syndrome. The pathogenesis of AIMBAD appears to be heterogeneous, as recent reports have demonstrated GIP-mediated hypercortisolism and familial AIMBAD. Transition from Cushing's disease to ACTH-independence is not supported by the available data. Future cases of AIMBAD should be investigated carefully to further elucidate the pathogenesis of this disorder. David Feldman, Division of Endocrinology, Dept. of Medicine, Room S-005, Stanford University Medical Center, Stanford, CA 94305, USA

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Spontaneous resolution of avascular necrosis of femoral heads following cure of Cushing’s syndrome

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-16-0015 ◽

2016 ◽

Vol 2016 ◽

Cited By ~ 1

Author(s):

A Pazderska ◽

S Crowther ◽

P Govender ◽

K C Conlon ◽

M Sherlock ◽

...

Keyword(s):

Femoral Head ◽

Avascular Necrosis ◽

Cushing’S Syndrome ◽

Cushing's Syndrome ◽

Leg Pain ◽

List Type ◽

Rapid Weight Gain ◽

Free Cortisol ◽

Femoral Heads ◽

Adrenal Disease

Summary Avascular necrosis (AVN) is a rare presenting feature of endogenous hypercortisolism. If left untreated, complete collapse of the femoral head may ensue, necessitating hip replacement in up to 70% of patients. The majority of the described patients with AVN due to endogenous hypercortisolaemia required surgical intervention. A 36-year-old female, investigated for right leg pain, reported rapid weight gain, bruising and secondary amenorrhoea. She had abdominal adiposity with violaceous striae, facial plethora and hirsutism, atrophic skin, ecchymosis and proximal myopathy. Investigations confirmed cortisol excess (cortisol following low-dose 48h dexamethasone suppression test 807nmol/L; 24h urinary free cortisol 1443nmol (normal<290nmol)). Adrenocorticotrophic hormone (ACTH) was <5.0pg/mL. CT demonstrated subtle left adrenal gland hypertrophy. Hypercortisolaemia persisted after left adrenalectomy. Histology revealed primary pigmented micronodular adrenal disease. Post-operatively, right leg pain worsened and left leg pain developed, affecting mobility. MRI showed bilateral femoral head AVN. She underwent right adrenalectomy and steroid replacement was commenced. Four months after surgery, leg pain had resolved and mobility was normal. Repeat MRI showed marked improvement of radiological abnormalities in both femoral heads, consistent with spontaneous healing of AVN. We report a case of Cushing’s syndrome due to primary pigmented nodular adrenocortical disease, presenting with symptomatic AVN of both hips. This was managed conservatively from an orthopaedic perspective. Following cure of hypercortisolaemia, the patient experienced excellent recovery and remains symptom free 4 years after adrenalectomy. This is the first report of a favourable outcome over long-term follow-up of a patient with bilateral AVN of the hip, which reversed with treatment of endogenous hypercortisolaemia. Learning points AVN of femoral head can be a presenting feature of hypercortisolism, both endogenous and exogenous. Rarely, treatment of hypercortisolaemia can reverse AVN without the need for orthopaedic intervention. Primary pigmented nodular adrenal disease is a rare cause of ACTH-independent Cushing’s syndrome.

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Cushing’s Syndrome Revealing Carney Complex: A Case Report

Endocrinology&Metabolism International Journal ◽

10.15406/emij.2017.05.00132 ◽

2017 ◽

Vol 5 (4) ◽

Author(s):

Hamza Elfekih

Keyword(s):

Case Report ◽

Cushing’S Syndrome ◽

Carney Complex ◽

Cushing's Syndrome

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Primary pigmented nodular adrenocortical disease and Cushing's syndrome

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302007000800009 ◽

2007 ◽

Vol 51 (8) ◽

pp. 1238-1244 ◽

Cited By ~ 16

Author(s):

Anelia Horvath ◽

Constantine Stratakis

Keyword(s):

Molecular Genetics ◽

Cushing’S Syndrome ◽

Adrenal Glands ◽

Skin Pigmentation ◽

Carney Complex ◽

Cushing's Syndrome ◽

Camp Signaling ◽

Camp Signaling Pathway ◽

Molecular Studies ◽

Adrenocortical Hyperplasia

Primary pigmented nodular adrenocortical disease (PPNAD) is a form of bilateral adrenocortical hyperplasia that is often associated with corticotrophin (ACTH)-independent Cushing's syndrome (CS) and is characterized by small to normal-sized adrenal glands containing multiple small cortical pigmented nodules (1,2). PPNAD may occur in an isolated form or associated with a multiple neoplasia syndrome, the complex of spotty skin pigmentation, myxomas, and endocrine overactivity, or Carney complex, in which Cushing's syndrome is the most common endocrine manifestation (3). Molecular studies have led to the identification of several genes, defects in which may predispose PPNAD formation; all of these molecules play important role for the cAMP signaling pathway. This review intends to present the most recent knowledge of the pathology and molecular genetics of the benign bilateral adrenocortical lesions, as well as to discuss the modern tools for diagnostics and treatment of this condition.

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