ACTH-Independent Cushing’s Syndrome: Primary Pigmented Nodular Adrenal Disease in the Context of Carney’s Complex

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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Is diabetes in Cushing's syndrome only a consequence of hypercortisolism?

Acta Endocrinologica ◽

10.1530/eje-13-0754 ◽

2014 ◽

Vol 170 (2) ◽

pp. 311-319 ◽

Cited By ~ 31

Author(s):

Carla Giordano ◽

Valentina Guarnotta ◽

Rosario Pivonello ◽

Marco Calogero Amato ◽

Chiara Simeoli ◽

...

Keyword(s):

Insulin Sensitivity ◽

Glucose Tolerance ◽

Cushing’S Syndrome ◽

Cushing's Syndrome ◽

Visceral Adiposity Index ◽

Metabolic Complications ◽

Family History Of Diabetes ◽

Pituitary Disease ◽

History Of ◽

Adrenal Disease

ObjectiveDiabetes mellitus (DM) is one of the most frequent complications of Cushing's syndrome (CS). The aim of this study was to define the changes in insulin sensitivity and/or secretion in relation to glucose tolerance categories in newly diagnosed CS patients.DesignCross-sectional study on 140 patients with CS.MethodsA total of 113 women (80 with pituitary disease and 33 with adrenal disease, aged 41.7±15.7 years) and 27 men (19 with pituitary disease and eight with adrenal disease, aged 38.1±20.01 years) at diagnosis were divided according to glucose tolerance into normal glucose tolerance (CS/NGT), impaired fasting glucose and/or impaired glucose tolerance (CS/prediabetes), and diabetes (CS/DM) groups.ResultsSeventy-one patients had CS/NGT (49.3%), 26 (18.5%) had CS/prediabetes and 43 (30.8%) had CS/DM. Significant increasing trends in the prevalence of family history of diabetes (P<0.001), metabolic syndrome (P<0.001), age (P<0.001) and waist circumference (P=0.043) and decreasing trends in HOMA-β (P<0.001) and oral disposition index (DIo) (P<0.002) were observed among the groups. No significant trends in fasting insulin levels, area under the curve for insulin (AUCINS), Matsuda index of insulin sensitivity (ISI-Matsuda) and visceral adiposity index were detected.ConclusionsImpairment of glucose tolerance is characterized by the inability of β-cells to adequately compensate for insulin resistance through increased insulin secretion. Age, genetic predisposition and lifestyle, in combination with the duration and degree of hypercortisolism, strongly contribute to the impairment of glucose tolerance in patients with a natural history of CS. A careful phenotypic evaluation of glucose tolerance defects in patients with CS proves useful for the identification of those at a high risk of metabolic complications.

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