Bilateral Nodular Adrenal Hyperplasia


I have a patient with bilateral nodular adrenal hyperplasia,.mildly elevated cortisol,but well apart from well controlled diabetes. What do I do ?

Surgery,medical therapy eg ketoconazole, nothing? Thanks. Steven Harris


Just having slightly enlarged nodular adrenals is not in itself a disease, and has to be seen in biochemical context. I would perform a dexamethasone suppression test for cortisol, preferably the full 2-day test, and measure plasma ACTH and 17-OH-progesterone. Assuming the patient suppresses their serum cortisol to <50 nmol/l and the 17-OH-P is normal, then I would do nothing. If the patient fails to suppress and the ACTH is readily detectable they will need a work-up for Cushing's disease. If the ACTH is undetectable then this may be a form of primary nodular adrenal disease and should be considered for medical-blocking therapy in the first instance followed by consideration of adrenalectomy. In general, if the patient is 'well' I would be more inclined to do less rather than more. Ashley Grossman, MD

Possible Precocious Puberty in an Infant


I have 7 months girl with a history of monthly vaginal bleeding for the last 3 months, without other signs of precocious puberty. pelvic US revealed multiple follicular appearance in both ovaries with following diameters of the ovaries : 0.9*1*1.5 cm. estradiol= 5 pg/ml. there are no other sources of the bleeding ( anal or others ) . how to manage this case/

thank you. Dr rasha ghazi ,Damascus,Syria


Dear Dr. Ghazi, Infrequently, an endocrine cause may pose as a local cause because of an absence of physical signs of puberty when bleeding starts as an apparently isolated phenomenon. Once you have ruled out malignant and benign lesions of the vagina, uterus and ovaries as well as foreign bodies in the vagina, traumatic lesions, and child abuse, specific causes include the following examples:

The newborn may have physiological vaginal (uterine estrogen withdrawal bleeding) bleeding and discharge (from the estrogenic vagina)

The first clinical sign of McCune-Albright syndrome is often vaginal bleeding. The diagnosis requires the characteristic cafè-au-lait pigmentation and radiological bone disease. Eventually secondary sexual development occurs. Careful follow-up is necessary because fibrous dysplasia may become apparent later in life.

Patients with isolated premature menarche may have isolated or recurrent vaginal bleeding without other signs of precocious puberty. This entity is usually benign and self-limiting and is thought to be the result of either a partial, transient activation of true precocious puberty or of an increased sensitivity of the endometrium to circulating levels of oestrogens which are too low to produce breast development. Careful evaluation and follow-up are required.

Prepubertal vaginal bleeding without signs of precocious puberty may be infrequently caused by prolonged, untreated hypothyroidism. I doubt this is the case in an infant with negative screening for congenital hypothyroidism.

Accidental estrogen ingestion, through maternal milk also, may set off vaginal bleeding without puberty development.

Sometimes, precocious puberty caused by a central nervous system lesion may have bleeding before secondary sexual development. Brain imaging is necessary for diagnosis. Let me know how the clinical picture evolve.

Dr Lucia Ghizzoni, Division of Endocrinology and Metabolism, Department of Internal Medicine

University of Turin,Corso Dogliotti 14, 10126 Turin, Italy