Pheochromocytoma is a neoplasm composed of cells similar to the chromaffin cells of the mature adrenal medulla. Pheochromocytomas occur in patients of all ages, and may be sporadic, or associated with a hereditary cancer syndrome , such as multiple endocrine neoplasia (MEN) types IIA and IIB, neurofibromatosis type I, or von Hippel-Lindau syndrome . Only 10% of adrenal pheochromocytomas are malignant , while the rest are benign tumors . The most clinically important feature of pheochromocytomas is their tendency to produce large amounts of the catecholamine hormones epinephrine (adrenaline) and norepinephrine . This may lead to potentially life-threatening high blood pressure , or cardiac arrythmias , and numerous symptoms such as headache , palpitations , anxiety attacks , sweating , weight loss , and tremor . Diagnosis is most easily confirmed through urinary measurement of catecholamine metabolites such as VMA and metanephrines . Most pheochromocytomas are initially treated with anti-adrenergic drugs to protect against catecholamine overload, with surgery employed to remove the tumor once the patient is medically stable.
The circadian pattern of cortisol release is controlled by the suprachiasmatic nucleus (SCN) of the hypothalamus, also known as the body clock. Nerve signals from the SCN cause the paraventricular nucleus (PVN) of the hypothalamus to release pulses of CRH roughly once per hour, resulting in HPA axis activation and cortisol release. There are also direct links between the SCN and the adrenal gland itself (bypassing the HPA axis) through sympathetic nerve fibres, causing the adrenal gland to become more sensitive to ACTH stimulation during the morning, further adding to the circadian pattern of cortisol release throughout the day.
Combined pituitary hormone deficiency (including ACTH deficiency) due to genetic pituitary abnormalities is rare. ACTH and cortisol deficiency have been described in patients with multiple pituitary hormone deficiencies due to mutations in the PROP-1 (Prophet of Pit-1) gene, even though PROP-1 is not expressed in corticotropes. The onset of cortisol deficiency, which may be severe, ranges from childhood to late adulthood [ 2-5 ]. Mutations in other transcription factors involved in early pituitary development (HESX1, LHX4) also can result in variable degrees of hypopituitarism that include ACTH deficiency [ 6,7 ]. (See "Causes of hypopituitarism", section on 'Genetic diseases' .)