Familial Cushing's Syndrome Research Articles

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

Two brothers (19 and 18 years old, respectively) presented with weight gain and stunted growth since the age of 10 years. They had spotty skin pigmentation over the face along with florid features of Cushing's syndrome with low bone density, renal calculi, dyslipidaemia, hypertension, and dilated cardiomyopathy. They underwent evaluation of the hypothalamic-pituitary-adrenals axis, which suggested ACTH-independent Cushing's syndrome, and the abdominal CT imaging revealed normal adrenals. The diagnosis of Familial Cushing's syndrome with primary pigmented nodular adrenal disease and Carney complex was made. Bilateral adrenalectomy was carried out in both of them with resolution of the features of hypercortisolaemia post-operatively.

Familial primary pigmented nodular adrenocortical disease without Carney complex (CNC): A case report and review of literature

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of familial Cushing's syndrome. It is characterized by bilateral adrenocortical hyperplasia with small to normal-sized adrenal glands containing multiple small adrenal cortical pigmented nodules [1,2]. PPNAD may occur in an isolated form or as familial PPNAD. Familial cases of PPNAD are usually associated with Carney complex in which Cushing’s syndrome is the most common endocrine manifestation [3]. Familial cases of PPNAD without associated Carney complex are very rare. Only a few cases of familial isolated PPNAD have been reported in the literature, mostly in females [4]. Isolated familial PPNAD has got a better prognosis than familial PPNAD associated with Carney Complex. This observation has important consequences for clinical management, follow-up and genetic counselling of such patients. Familial cases of PPNAD are rare and mostly present in females with associated Carney complex. We herein report a case of familial Cushing’s syndrome in male siblings due to PPNAD without associated Carney complex.

Maladie de Cushing et adénome cortico-surrénalien: Deux associations étonnantes

Cushing's syndrome has a very low incidence (1-10 cases/million/year), and familial cases are even more rare. We report on two situations involving different causes of Cushing's syndrome.In the first case, we describe the case of a patient with an adrenal adenoma 20 years before the occurrence of Cushing's disease related to the pineal gland. In the second case, two members of the same family were diagnosed almost simultaneously with adrenal cortical adenoma (mother) and Cushing's disease (daughter).These cases lead us to consider the known causes of familial Cushing's syndrome, which were not found here.

Familial ACTH-independent Cushing's syndrome with bilateral macronodular adrenal hyperplasia clinically affecting only female family members.

Primary adrenal hyperplasia, which may occur as a familial disorder, is a rare cause of ACTH-independent Cushing's syndrome. In most of these cases the underlying pathology is primary adrenocortical micronodular dysplasia. Very few cases of familial Cushing's syndrome due to primary macronodular adrenal hyperplasia have been described. We report a family with seven affected family members. The pedigree indicates an autosomal dominantly inherited disorder. Interestingly only female family members developed the clinically apparent syndrome. The only available obligatory male gene carrier failed to adequately suppress his plasma cortisol level on overnight dexamethasone suppression test. His adrenal glands showed nodular enlargement on abdominal computed tomographic imaging. Screening of the MEN 1 gene and genetic analysis of the hot spot regions of the GNAS 1 (codons 201 and 227) and GNAI 2 (codons 179 and 205) genes did not show any mutations in the constitutional DNA or the adrenal tissue DNA of the index patient. In conclusion, this family is the largest kindred reported in the literature with ACTH-independent Cushing's syndrome due to autosomal dominant inherited macronodular adrenocortical hyperplasia. Four currently alive and affected family members in two generations and further careful observation of the yet unaffected members of the third available generation might offer the opportunity to identify the still unknown gene defect in the future.

Familial Cushing's syndrome due to nodular adrenocortical dysplasia is an inherited disease of immunological origin.

Circulating immunoglobulins may be involved in the pathogenesis of familial Cushing's syndrome due to nodular adrenocortical dysplasia. The disease may also be part of a complex including cutaneous and cardiac myxomas, spotty pigmentation of the skin, and other signs of endocrine overactivity. In the present study of two sisters treated by complete adrenalectomy for Cushing's syndrome due to nodular adrenocortical dysplasia, and of their first-degree relatives, no evidence of associated disorders was present. However, the serum of both girls and of their mother contained immunoglobulins capable of stimulating adrenal DNA synthesis and cortisol production in vitro. The study supports the theory that familial Cushing's syndrome due to adrenocortical dysplasia is an inherited disease of immunological origin.

FAMILIAL CUSHING'S SYNDROME DUE TO NODULAR ADRENOCORTICAL DYSPLASIA. A PUTATIVE RECEPTOR‐ANTIBODY DISEASE?

Two sisters aged 13 and 19 years suffering from familial Cushing's syndrome due to nodular adrenocortical dysplasia are described. Pituitary adrenocortical function tests indicated the presence of adrenal autonomy. Adrenal scintigraphy showed bilateral symmetrical uptake indicating the bilateral character of the autonomous process. Complete adrenalectomy was performed in both girls. The adrenals were of about normal weight showing numerous dark brown pigmented nodules and small perivascular lymphocytic infiltrates. Serum immunoglobulin preparations obtained from both girls stimulated adrenocortical cell growth in a cytochemical bioassay system. It is proposed that circulating growth factors may be involved in the pathogenesis of the disease.

Familial Cushing's syndrome due to pigmented multinodular adrenocortical dysplasia

Cushing's syndrome was diagnosed in a 14 year old girl and, 5 years later, in her nephew (sister's son) also when he was 14 years of age. Administration of tetracosactid (Synacthen) did not stimulate adrenocortical function in either patient, nor did dexamethasone suppress the elevated urinary steroids in the girl, and only partially suppressed them in the boy. Both patients were adrenalectomized and made an uneventful recovery. The surgical specimens were identical both on gross inspection and histologically, showing the typ ical morphological features of pigmented multinodular adrenocortical dysplasia. We believe that this lesion represents an inherited adrenocortical maldevelopment (rather than true neoplasia) leading to an autonomous adrenocortical hyperfunction which typically manifests itself clinically during adrenarche (i.e. functional adrenocortical maturation) at the beginning of puberty. Family Cushing's syndrome, caused by pigmented multinodular adrenocortical dysplasia, represents a disease entity.