Regardless of the adenomas location, most patients require steroid replacement postoperatively at least in the interim, as long-term suppression of pituitary ACTH and normal adrenal tissue does not recover immediately. Clearly, if both adrenals are removed, replacement with hydrocortisone or prednisolone is imperative.In those patients not suited for or unwilling to undergo surgery, several drugs have been found to inhibit cortisol synthesis (e.g. ketoconazole, metyrapone) but they are of limited efficacy. Mifepristone is a powerful glucocorticoid type II receptor antagonist and, since it does not interfere with normal cortisol homeostasis type I receptor transmission, may be especially useful for treating the cognitive effects of Cushings syndrome. However, the medication faces considerable controversy due to its use as an abortifacient. In February 2012, the FDA approved mifepristone to control high blood sugar levels (hyperglycemia) in adult patients who are not candidates for surgery, or who did not respond to prior surgery, with the warning that mifepristone should never be used by pregnant women- although pregnancy is extremely rare during the course of Cushings Syndrome  In March 2020, Isturisa (osilodrostat) oral tablets a 11-beta-hydroxylase enzyme inhibitor was approved by FDA for treating those patients who cannot undergo pituitary surgery or for patients who underwent surgery but continue to have the disease.Removal of the adrenals in the absence of a known tumor is occasionally performed to eliminate the production of excess cortisol. In some occasions, this removes negative feedback from a previously occult pituitary adenoma, which starts growing rapidly and produces extreme levels of ACTH, leading to hyperpigmentation.
A voice change or voice mutation, sometimes referred to as a voice break or voice crack, commonly refers to the deepening of the voice of people as they reach puberty. Before puberty, both sexes have roughly similar vocal pitch, but during puberty the male voice typically deepens an octave, while the female voice usually deepens only by a few tones.A similar effect is a "voice crack", during which a persons voice suddenly and unintentionally enters a higher register (usually falsetto) for a brief period of time. This may be caused by singing or talking at a pitch outside the persons natural vocal range, stress, fatigue, emotional tension, or the physical changes associated with puberty. An instance of a voice crack (when associated with puberty) lasts for only a moment and generally occurs less frequently as a person grows into maturity. Anatomical changes
Most of the voice change begins around puberty. Adult pitch is reached 2–3 years later but the voice does not stabilize until the early years of adulthood. It usually happens months or years before the development of significant facial hair. Under the influence of sex hormones, the voice box, or larynx, grows in both sexes. This growth is far more prominent in males than in females and is more easily perceived. It causes the voice to drop and deepen. Along with the larynx, the vocal folds (vocal cords) grow significantly longer and thicker. The facial bones begin to grow as well.