Update on primary micronodular bilateral adrenocortical diseases.

PURPOSE OF REVIEW: Primary micronodular bilateral adrenocortical hyperplasias (MiBAH) are rare challenging diseases. Important progress in understanding its pathophysiology and genetics occurred in the last two decades. We summarize those progress and recent data on investigation and therapy of MiBAH focusing on primary pigmented nodular adrenocortical disease (PPNAD). RECENT FINDINGS: Larger recent cohorts of PPNAD patients from various countries have confirmed their variable Cushing's syndrome phenotypes. Age of onset is earlier than other ACTH-independent Cushing's syndrome causes and the youngest case have now occurred at 15 months. Two retrospective studies identified an increased risk of osteoporotic fractures in PPNAD as compared with other Cushing's syndrome causes. The utility of 6-day oral dexamethasone test to produce a paradoxical increase of urinary-free cortisol in PPNAD was confirmed but the mean fold of increase was of 48%, less than previously suggested. Several new genetic variants of the PRKAR1A gene have been reported in PPNAD or Carney complex (CNC). Remission of Cushing's syndrome with unilateral adrenalectomy was reported in a few patients with PPNAD. SUMMARY: MiBAH, PPNAD and CNC are rare challenging diseases, but with combined expert clinical and genetic approaches a comprehensive investigation and prevention strategy can be offered to affected patients and families.

ARMC5 Mutations in a Large Cohort of Primary Macronodular Adrenal Hyperplasia: Clinical and Functional Consequences.

CONTEXT: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of primary adrenal Cushing's syndrome (CS). ARMC5 germline mutations have been identified recently in PBMAH. OBJECTIVE: To determine the prevalence of ARMC5 mutations and analyze genotype-phenotype correlation in a large cohort of unrelated PBMAH patients with subclinical or clinical CS. PATIENTS AND METHODS: ARMC5 was sequenced in 98 unrelated PBMAH index cases. PBMAH was identified by bilateral adrenal nodular enlargement on computed tomography scan. The effect on apoptosis of ARMC5 missense mutants was tested in H295R and HeLa cells. Clinical and hormonal data were collected including midnight and urinary free cortisol levels, ACTH, androgens, renin/aldosterone ratio, cortisol after overnight dexamethasone suppression test, cortisol and 17-hydroxyprogesterone after ACTH 1-24 stimulation and illegitimate receptor responses. Computed tomography and histological reports were analyzed. RESULTS: ARMC5-damaging mutations were identified in 24 patients (26%). The missense mutants and the p.F700del deletion were unable to induce apoptosis in both H295R and HeLa cell lines, unlike the wild-type gene. ARMC5-mutated patients showed an overt CS more frequently, compared to wild-type patients: lower ACTH, higher midnight plasma cortisol, urinary free cortisol, and cortisol after dexamethasone suppression test (P = .003, .019, .006, and <.001, respectively). Adrenals of patients with mutations were bigger and had a higher number of nodules (P = .001 and <.001, respectively). CONCLUSIONS: ARMC5 germline mutations are common in PBMAH. Index cases of mutation carriers show a more severe hypercortisolism and larger adrenals. ARMC5 genotyping may help to identify clinical forms of PBMAH better and may also allow earlier diagnosis of this disease.

Adrenal cytomegaly is a frequent pathologic finding in hemoglobin bart hydrops fetalis.

Adrenocortical cytomegaly (AC) is a relatively uncommon phenomenon but tends to occur in certain situations, including specific congenital anomalies and hydrops due to maternal-fetal Rhesus incompatibility. Because the pathology in the latter condition does not differ greatly from hemoglobin (Hb) Bart hydrops fetalis, we performed a retrospective review of fetal and perinatal autopsy cases with Hb Bart to determine the prevalence of AC in that condition. Over a 10-year period (2001-2010) at King Chulalongkorn Memorial Hospital, there were 16 hydropic cases confirmed to have Hb Bart. Adrenocortical cytomegaly was found in 13 cases (81%). For comparison, we determined the occurrence of AC in cases of hydrops fetalis not due to Hb Bart (n  =  33) and a heterogeneous group of congenital anomalies (n  =  34). Adrenocortical cytomegaly was identified in only 1 case of Beckwith-Wiedemann syndrome and 2 cases of anencephaly. Thus, AC is a common finding in cases of Hb Bart, a finding not previously documented. Moreover, our study suggests that Hb Bart is one of the conditions most commonly associated with AC. The reasons for this are not known. The mean Hb levels for the hydrops cases with Hb Bart and those with other forms of anemia showed no significant difference (P  =  0.63), nor was there any significant difference in Hb levels between cases of Hb Bart with and without AC. Nonetheless, the consistency of AC in cases of Hb Bart suggests that further study of this particular group of patients might shed light on the pathogenesis of this poorly understood pathologic finding.

Manejo de la patología suprarrenal en Atención Primaria / Management of adrenal disorders in primary care

Las glándulas suprarrenales constituyen un órgano par situado en el espacio retroperitoneal superpuestas al polo superior renal. En las suprarrenales se distinguen 2 unidades funcionales: la corteza y la médula, con distinto origen embriológico. Las suprarrenales constituyen un sistema hormonal que regula numerosas funciones esenciales para el organismo. Los glucocorticoides tienen efectos sobre el metabolismo, sistema inmunológico, procesos de crecimiento, los mineralocorticoides controlan el balance del sodio y el potasio, regulando la presión arterial y los andrógenos suprarrenales contribuyen a la iniciación de la pubertad. En la médula adrenal se sintetizan catecolaminas que intervienen en el control de la tensión arterial y respuesta ante el estrés. El objetivo de este artículo es realizar una revisión práctica de los principales cuadros clínicos de la patología suprarrenal y que con más frecuencia se pueden observar dentro del ámbito de la Atención Primaria(AU)

The adrenal glands are made up by a paired organ in the retroperitoneal space overlapping the upper pole of the kidney. Two functional units are distinguished in the adrenal glands: the cortex and medulla, with different embryological origin. The adrenal glands make up a hormone system that regulates many essential functions for the body. The glucocorticoids have effects on the metabolism, immune system, growth processes, the mineral corticosteroids control the sodium and potassium balance, regulating the blood pressure and the adrenal androgens contribute to the initiation of puberty. In the adrenal medulla, catecholamines are synthesized, these participating in the blood pressure control and the response to stress. This article has aimed to perform a practical review of the principal clinical pictures of the adrenal disorders and that are observed within the Primary Care setting more frequently(AU)

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.

CONTEXT: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is known as a rare hereditary disease with classic triad of mucocutaneous candidiasis, hypoparathyroidism, and adrenocortical failure, two of which, diagnostic dyad, are required for the diagnosis. Evidently many patients suffer unrecognized because the condition is more variable and complex. OBJECTIVE: The objective of the study was to describe the variability of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy for promoting recognition and adequate follow-up of patients. SETTING: The Finnish series of patients is the largest internationally. PATIENTS: The study population was all 91 known Finnish patients. RESULTS: Besides the classical triad, a dozen autoimmune endocrine and other components occurred variably, several of them dangerous. The initial manifestation appeared within the age range of 0.2-18 yr, mucocutaneous candidiasis being part of it in 60% of the patients, hypoparathyroidism in 32%, and adrenocortical failure in 5%. But 23% of the patients had one to six other components before the diagnostic dyad: hepatitis, keratoconjunctivitis, chronic diarrhea, periodic rash with fever. The dyad appeared 0.2-20 yr later. Prevalence of most components increased with age, diabetes mellitus, hypothyroidism, and testicular failure becoming common toward middle age. Tubulointerstitial nephritis occurred in 9% of the patients, apparent mineralocorticoid excess in 9%, asplenia in 19% of adults, and oral or esophageal squamous cell carcinoma in 10% of patients older than 25 yr. CONCLUSIONS: Any child or young adult with one of the many disease components should be examined for others and consideration of AIRE mutation assay.

Adrenal disorders in cats.

Although adrenal disorders are uncommon in cats, they are being recognized with increasing frequency. The low incidence and unique characteristics of adrenal disease in cats often make the diagnosis and treatment of these disorders challenging. This article summarizes information on the diagnosis and treatment of feline adrenal disorders, including hyperadrenocorticism, hypoadrenocorticism, pheochromocytoma, and hyperaldosteronism.