Cortisol producing adenomas

Orpha code: 443287

Cortisol producing adenomas (CPA) are benign tumors of the adrenal cortex that are characterised by an autonomous secretion of the main glucocorticoid cortisol. Acquired (somatic) mutations in the PRKACA gene have been identified in the majority of cases as the molecular cause of hormonal oversecretion. The primary therapy is surgical resection by unilateral adrenalectomy. Following surgery adrenal insufficiency will occur that will require – at least temporarily – glucocorticoid substitution therapy.

Adrenocortical carcinoma

Orpha code: 1501

Adrenocortical carcinoma (ACC) is a cancer that arises from the adrenal cortex. Adrenocortical carcinoma occurs in childhood with a peak incidence at 3.5 years of age. Most ACCs in children and adolescents are hormone-secreting and the clinical presentation reflects the pattern of adrenocortical hormones secreted by the tumor. In adults, ACC can occur at any age with a female predominance. Most often hypercortisolism and/or hyperandrogenism are present. Endocrine inactive ACCs are rare but might require specialized endocrine analysis to pick up output of steroid precursors. Surgery is the mainstay of therapy in amendable cases while adrenolytic medical therapy, chemotherapy alone or in combination with local radiation are required in many cases.

Primary bilateral macronodular hyperplasia

Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a disease that is characterised by the slow development of large nodules in both adrenal glands with adult onset of hypercortisolism that has been associated with germline mutations in ARMC5 in the majority of cases. Due to a proposed impact of adrenal derived ACTH to the hormonal activity of the adrenal nodules the earlier term ACTH independent macronodular hyperplasia has been abandoned. While the illicit presence of peptide receptors in the adrenal nodules can result in specific disease manifestation (such as food dependent Cushing’s syndrome) and might offer medical therapeutic options, in most cases surgical therapy of the dominant side or bilaterally is the treatment of choice.

Primary pigmented nodular adrenocortical disease

Primary pigmented nodular adrenocortical disease (PPNAD) is a form of bilateral adrenocortical hyperplasia that is often associated with ACTH independent Cushing syndrome and small to normal sized adrenal glands containing multiple small cortical pigmented nodules. In the vast majority of cases PPNAD occur as one of the manifestations of Carney complex. The condition is inherited in an autosomal dominant manner and can be associated with mutations in the PRKAR1A, PDE11A and PDE8B genes that all affect pathways that are associated with glucocorticoid output. Bilateral adrenalectomy is the most common treatment for CS due to PPNAD followed by life-long cortisol and mineralocorticoid supplementation

Adrenal Insufficiency

Orpha code: 101959

Chronic primary adrenal insufficiency (CPAI) is a chronic disorder of the adrenal cortex resulting in the inadequate production of glucocorticoid and mineralocorticoid hormones.Disease onset peaks around 40 but can occur at any age. It presents insidiously with nonspecific symptoms that can be mistaken for other more prevalent conditions. Common manifestations include fatigue, loss of energy, malaise, weight loss, nausea, anorexia (failure to thrive in children), muscle and joint pain.

Congenital adrenal hyperplasia

Orpha code: 418

Congenital adrenal hyperplasia (CAH) is an inherited endocrine disorder caused by a steroidogenic enzyme deficiency that is characterised by adrenal insufficiency and variable degrees of hyper or hypo androgeny manifestations, depending of the type and the severity of the disease. Girls present at birth with ambiguous genitalia and variable levels of virilization. They have a normal uterus but abnormal vaginal development. The external genitalia in boys are normal. Salt wasting forms of CAH lead to symptoms of dehydration and hypotension in the first few weeks of life and can be life threatening. Premature pubarche can be seen in children as well as accelerated growth velocity and accelerated skeletal maturation (leading to short stature in adulthood).NCAH is often not diagnosed until adolescence when the first symptoms appear. Manifestations seen in females are hirsutism, acne, anovulation and menstrual irregularities. Males (and some females) are asymptomatic. Hirsutism continues in adulthood and women can suffer from chronic anovulation and fertility problems. Other rare forms can present with arterial hypertension, craniofacial malformations and sexual ambiguity in both sexes.

Familial Hyperaldosteronism

Orpha code: 235936

Familial hyperaldosteronism (FH) is the heritable form of primary aldosteronism (PA) which comprises three identified subtypes to date: FH type I (FH-I; see this term) characterised by early-onset hypertension, glucocorticoid remediable adrenocorticotropic hormone (ACTH)-dependent hyperaldosteronism, variable hypokalemia, and overproduction of 18-oxocortisol and 18-hydroxycortisol; FH type II (FH-II; see this term) characterised by hypertension of varying severity and hyperaldosteronism not suppressible by dexamethasone; and FH type III (FH-III; see this term) characterised by profound hypokalemia, early-onset severe hypertension, non glucocorticoid-remediable hyperaldosteronism, and overproduction of 18-oxocortisol and 18-hydroxycortisol.