Primary pigmented nodular adrenocortical disease associated with Carney complex: case report and literature review.

CONTEXT: Carney complex (CNC), a familial multiple neoplasm syndrome with dominant autosomal transmission, is characterized by tumors of the heart, skin, endocrine and peripheral nervous system, and also cutaneous lentiginosis. This is a rare syndrome and its main endocrine manifestation, primary pigmented nodular adrenal disease (PPNAD), is an uncommon cause of adrenocorticotropic hormone-independent Cushing's syndrome. CASE REPORT: We report the case of a 20-year-old patient with a history of weight gain, hirsutism, acne, secondary amenorrhea and facial lentiginosis. Following the diagnosing of CNC and PPNAD, the patient underwent laparoscopic bilateral adrenalectomy, and she evolved with decreasing hypercortisolism. Screening was also performed for other tumors related to this syndrome. The diagnostic criteria, screening and follow-up for patients and affected family members are discussed.

Mutations of the PRKAR1A gene in Cushing's syndrome due to sporadic primary pigmented nodular adrenocortical disease.

Primary pigmented nodular adrenocortical disease (PPNAD) is a cause of ACTH-independent Cushing's syndrome. This condition can be difficult to diagnose because hypercortisolism may be periodic and adrenal imaging may not demonstrate an adrenal tumor. PPNAD can be part of the Carney complex (CNC), an autosomal dominant multiple neoplasia syndrome. Germline mutations of the regulatory subunit R1A of PKA (PRKAR1A) have been observed in about 45% of CNC kindreds. To improve our understanding of sporadic PPNAD and develop a potential diagnostic tool, we investigated the genetics of patients with sporadic and isolated PPNAD. Patients undergoing surgery for bilateral ACTH-independent Cushing's syndrome in whom pathological examination revealed PPNAD were subjected to endocrinological investigations and a systematic search for other manifestations of CNC. The PRKAR1A gene was sequenced using DNA from frozen adrenal tissues and leukocytes from three patients with sporadic isolated PPNAD and using leukocyte DNA from two additional patients. Different inactivating germline mutations of the PRKAR1A gene were found in the five patients. For three cases, study of the parents' DNA demonstrated a de novo mutation. One patient presented with an unusual 2.5-cm macronodule of the right adrenal mimicking an adrenal adenoma. A somatic 16-bp deletion of PRKAR1A gene was also found in this macronodule. Inactivating germline mutations of PRKAR1A are frequent in sporadic and isolated cases of PPNAD. The wild-type allele can be inactivated by somatic mutations, consistent with the hypothesis of the gene being a tumor suppressor gene. Thus, genetic analysis can be of help to the clinician in the diagnosis of this difficult form of adrenal Cushing's syndrome.

[Bilateral adrenal hemorrhage occurring two times in primary antiphospholipid syndrome (APS). Anticoagulation as treatment of hemorrhage]. / Zweizeitige bilaterale Nebennierenblutung bei primärem Antiphospholipidsyndrom (APS) - "Antikoagulation als Therapie der Blutung" -

HISTORY: A 56-year-old man was admitted for investigation of abdominal pain radiating to the back. The patient was known to suffer from APS and autoimmune thrombocytopenia, and was therefore treated with oral anticoagulants. The clinical examination was normal. INVESTIGATIONS: Ultrasound detected an area with low echogenicity in the region of the right adrenal gland. A CAT scan identified this mass as an adrenal hemorrhage. DIAGNOSIS AND TREATMENT: Anticoagulation treatment was discontinued because the bleeding and thrombocytopenia and the patient's pain subsided. A few days later, he experienced similar pain, this time radiating to the left side. A second hematoma was discovered in the left adrenal gland. The patient developed symptoms of acute adrenal insufficiency, which subsided after therapy. The bilateral adrenal hemorrhage was considered to be secondary bleeding following thromboses in the venous system of the adrenal gland. The thromboses were due to the underlying APS. Anticoagulation therapy was resumed, and the patient's condition stabilised without further complications. CONCLUSION: The cessation of anticoagulation therapy in this patient paradoxically led to hemorrhage, this time of the contralateral adrenal gland. Unilateral and, especially, bilateral adrenal bleeding should give rise to the suspicion of thrombophilic disorders such as APS or heparin-induced thrombocytopenia (HIT); for which careful anticoagulation is the treatment of choice.

Frequency of pulmonary mineralization and hypoxemia in 21 dogs with pituitary-dependent hyperadrenocorticism.

The purpose of this study was to determine the frequency of hypoxemia and pulmonary mineralization using 99mTc-methylene diphosphonate (99mTc-MDP) in dogs with pituitary-dependent hyperadrenocorticism (PDH). Twenty-one dogs with PDH were prospectively evaluated using thoracic radiography, arterial blood gas analysis, and bone phase and pulmonary perfusion scintigraphy (using 99mTc-macro-aggregated albumin [99mTc-MAA]). The radiographs and bone and perfusion studies were evaluated subjectively. An averaged quantitative count density ratio was calculated between the thorax and cranial thoraco-lumbar vertebrae from lateral thoracic 99mTc-MDP images. Thoracic:vertebral ratios were calculated using 99mTc-MDP studies from 21 control dogs. The thoracic:vertebral ratios were compared between the 2 groups (PDH and control). The mean age (+/-SD) of the 21 PDH dogs was 10.2 (+/-3) years, whereas the mean age of the control group was 9.8 (+/-3) years. Seven of the 21 dogs with PDH were hypoxemic (defined as an arterial partial pressure of oxygen [PaO2] < 80 mm Hg) with an average PaO2 (+/-SD) of 62 (+/-15) mm Hg. Of the 7 hypoxemic dogs, 2 were found to have pulmonary mineralization based on bone scintigraphic images. Pulmonary perfusion abnormalities were not identified using 99mTc-MAA in any of the 21 PDH dogs. Six PDH dogs had an abnormal interstitial pulmonary pattern and 5 of these dogs were hypoxemic. The average quantitative thoracic:vertebral ratio was not significantly different between the PDH and control dogs (0.5 +/- 0.4 versus 0.4 +/- 0.1, P = .16). Causes of hypoxemia other than pulmonary thromboembolism should be considered in dogs with PDH. Pulmonary mineralization may contribute to hypoxemia in dogs with PDH.

Radionuclide imaging of the adrenal cortex.

Adrenocortical scintigraphy provides information concerning cortical function that is not readily available by other means. The ability to map differential adrenal cortical function has great clinical utility and demonstrable cost-effectiveness in the evaluation of adrenocortical disease and in distinguishing benign from malignant lesions in patients with incidentally discovered adrenal masses.

Adrenal hemorrhage diagnosed by ultrasonically-guided biopsy.

Adrenal hemorrhage in adults is an uncommon disease and is usually associated with systemic diseases, trauma or anticoagulation. When adrenal hemorrhage is discovered in chronic course without any suggestive clinical settings, it is difficult to distinguish adrenal hemorrhage correctly before surgical resection. We present a case of adrenal hemorrhage which was incidentally detected as an adrenal mass and was successfully treated in a conservative way based upon histopathological findings obtained by ultrasonically guided biopsy.

Primary pigmented nodular adrenocortical disease: reevaluation of a patient with carney complex 27 years after unilateral adrenalectomy.

A 45-yr-old man with primary pigmented nodular adrenocortical disease (PPNAD) is described. This patient underwent unilateral adrenalectomy for ACTH-independent Cushing's syndrome (CS) in 1969. Although his daily urinary free cortisol (UFC) excretion rate normalized, and the major clinical manifestations of CS subsided, loss of a circadian cortisol rhythm persisted after surgery. Twenty-seven years later, the patient presented again with short stature, severe osteopenia, skeletal deformities, thinning of the skin, and myopathy.

Bilateral massive adrenal haemorrhage complicating anaphylactic shock: a case report.

A case of bilateral adrenal haemorrhage complicating anaphylactic shock is reported. Hypovolemic shock related to peritoneal haemorrhage was the main feature landing to laparotomy. Ultrasonographic examination was not contributive, but CT scan easily documented the adrenal haemorrhage and must be considered a valuable diagnostic tool when adrenal haemorrhage is suspected.

Adrenal cortical and medullary imaging.

Adrenal disease can be manifested by endocrine dysfunction or anatomic abnormalities detected by cross-sectional imaging modalities. With the advent of newer and more reliable in vitro assays and a better understanding of the spectrum of adrenal pathology, the physician can now adopt a more accurate and cost-effective approach to the diagnosis of adrenal disease. Both functional and anatomic imaging modalities can play an important role in the evaluation of the incidental adrenal mass, the early detection of adrenal metastases, differentiation of the various causes of Cushings's syndrome, selection of patients for potentially curative surgery in primary aldosteronism and adrenal hyperandrogenism, and localization of pheochromocytomas and neuroblastomas. The usefulness of the adrenal cortical radiopharmaceutical, 131I-6-beta-iodomethylnorcholesterol (NP-59), and the adrenal medullary radiopharmaceuticals, 131I and 123I-metaiodobenzylguanidine (MIBG), is detailed for these various clinical settings and the role of NP-59 and MIBG is contrasted to that of the cross-sectional modalities, computed tomography and magnetic resonance imaging (MRI). Incidental adrenal masses are common, but malignancies are few. Imaging studies select those patients who require a further evaluation by biopsy examination or adrenalectomy. In the hyperfunctioning endocrine states, such as Cushing's syndrome, primary aldosteronism, adrenal androgenism, and pheochromocytoma, correlation of biochemical findings with both functional and anatomic imaging is necessary to avoid inappropriate and ineffective surgical intervention, yet not miss an opportunity for curative resection. Lastly, MIBG and MRI are complementary in the detection and staging of neuroblastoma.

Congenital nephrosis in association with hypothyroidism and hypoadrenocorticism.

Adrenal abnormalities are rarely recognized in association with the nephrotic syndrome. This report describes the hospital course of an 11-week-old child with congenital nephrotic syndrome secondary to diffuse mesangial sclerosis, in addition to hypothyroidism and hypoadrenocorticism.

Benign hemorrhagic adrenocortical macrocysts in Beckwith-Wiedemann syndrome.

A new pseudotumorous lesion found in the adrenal cortex of six infants with Beckwith-Wiedemann syndrome is described. These cystic masses were discovered either prenatally by using sonography or early in the neonatal period as palpable flank masses. Imaging studies, including sonography and CT, could not confidently exclude malignancy. After the masses were removed surgically, histologic examination showed them all to be benign hemorrhagic macrocysts within the capsule or permanent cortex (in contrast to neonatal adrenal hemorrhage, which usually occurs more centrally in the fetal cortex). The cysts were as large as 8 cm in diameter, and in one case a solitary cyst was predominant. Hemihypertrophy was present in all cases. Four of the six lesions were right-sided, and there was a male-female ratio of 5:1. Benign hemorrhagic adrenocortical macrocysts are a cause of abdominal mass in the fetus and neonate with Beckwith-Wiedemann syndrome.

Cushing syndrome due to primary pigmented nodular adrenocortical disease: findings at CT and MR imaging.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing syndrome in infants, children, and young adults. It is characterized by non-adrenocorticotropic hormone-dependent hypersecretion of cortisol by multiple, pigmented nodules of hyperplastic adrenocortical cells. With a single exception, adrenal glands have been described as normal with computed tomography (CT) in all previous series. Eight patients had Cushing syndrome due to surgically proved PPNAD. Four of the eight patients had stigmas of Carney complex (lentigines, calcified Sertoli cell tumors of the testes, and cardiac and soft-tissue myxomas). CT and/or magnetic resonance (MR) imaging demonstrated unilateral or bilateral nodularity in five of six patients examined. Macronodules (greater than 10 mm) were seen in the two oldest patients. As the clinical presentation of Cushing syndrome in this group of patients may be atypical (severe osteoporosis or short stature), the detection of multiple, small adrenocortical nodules with CT or MR imaging supports, or may even suggest, the diagnosis of PPNAD.

Marked elevation of serum dehydroepiandrosterone sulphate in Cushing's disease with macronodular adrenocortical hyperplasia.

A 30-year-old man presented with longstanding hypercortisolism and biochemical studies typical of pituitary-dependent Cushing's disease. After unsuccessful transsphenoidal surgery, plasma ACTH transiently became undetectable and adrenal computed tomography (CT) was consistent with macronodular hyperplasia. Serum dehydroepiandrosterone sulphate (DHEA-S) exceeded 10,000 ng/ml (normal 2,000-3,350 ng/ml). Despite either transient adrenal autonomy or variable adrenocortical ACTH hyperresponsiveness, urinary cortisol normalized within eight months following pituitary irradiation alone. Serum DHEA-S fell progressively but remained mildly elevated (4,000 ng/ml). Follow-up CT showed minimal residual adrenal nodularity. Given these findings and a review of the literature, we propose that chronic cosecretion of non-ACTH proopiomelanocortinderived peptides may have stimulated both hypersecretion of DHEA-S and adrenocortical macronodularity in this patient.

[Spongiocytic adenoma of the adrenal cortex--risk of misinterpretation as a cyst in computerized tomography]. / Spongiozytäre Nebennierenrindenadenome--Gefahr einer Fehldeutung als Zyste im CT.

A report on two cases where solid benign tumours of the adrenals (spongiocytic adrenocortical adenomas) were misinterpreted as adrenal cysts due to water-equivalent density values. The CT scans are compared with the microscopic cuts.