The 40-year-old woman shown below complains of weakness, amenorrhea, and easy bruisability. She has hypertension and diabetes mellitus. She denies use of any medications other than hydrochlorothiazide and metformin.
What is the most likely explanation for her clinical findings?
The clinical findings all suggest an excess production of cortisol by the adrenal gland. Hypertension, truncal obesity, and dark abdominal striae are common physical findings; patients often have ecchymoses at points of trauma (especially legs and forearms) because of increased capillary fragility. The process responsible for hypercortisolism is most often an ACTH-producing pituitary microadenoma. An adrenal adenoma that directly produces cortisol is the next most likely option. Most ectopic ACTH-producing neoplasms (usually small cell carcinoma of the lung) progress too rapidly for the full Cushing syndrome to develop. These patients usually present with muscle weakness due to profound hypokalemia. The initial test to diagnose endogenous cortisol overproduction is either the overnight dexamethasone suppression test (in normals, the AM cortisol should suppress to < 2 μg/dL after a midnight dose of 1 mg dexamethasone) or 24-hour urine collection for free cortisol. More extensive testing is then required to determine the source. Hypothalamic tumors can affect ADH production and eating behavior but do not produce cortisol or ACTH. Unexpected bruising should prompt questions about domestic violence, but partner abuse would not account for the constellation of this patient’s findings.
A 24-year-old man presents with gynecomastia and infertility. On examination, he has small, firm testes and eunuchoid features. He has scant axillary and pubic hair. Which of the following is correct?
The picture of infertility, gynecomastia, and tall stature (arms and legs longer than expected for truncal size) is consistent with Klinefelter syndrome and an XXY karyotype. The patient has abnormal gonadal development with hyalinized testes that result in low testosterone levels. Pituitary function in Klinefelter syndrome is normal, so gonadotropin levels are elevated in response to underproduction of testosterone. Although Klinefelter patients may have sexual function, they do not produce sperm and are infertile. Turner syndrome refers to the 45 XO karyotype that results in abnormal sexual development in a female.
A 52-year-old man complains of impotence. On physical examination, he has an elevated jugular venous pressure, S3 gallop, and hepatomegaly. He also appears tanned, with pigmentation along joint folds. His left knee is swollen and tender. The plasma glucose is 250 mg/dL, and liver enzymes are elevated. Which of the following studies will help establish the diagnosis?
Iron overload should be considered among patients who present with any one or a combination of the following: hepatomegaly, weakness, hyperpigmentation, atypical arthritis, diabetes, impotence, unexplained chronic abdominal pain, or cardiomyopathy. Diagnostic suspicion should be particularly high when the family history is positive for similar clinical findings. The most frequent cause of iron overload is the common genetic disorder, idiopathic hemochromatosis. Secondary iron storage problems can occur after multiple transfusions in a variety of anemias. The most practical screening test is the determination of serum iron, transferrin saturation, and ferritin. Transferrin saturation greater than 50% in males or 45% in females suggests increased iron stores. Substantially elevated serum ferritin levels confirm total body iron overload. Genetic screening is now used to assess which patients are at risk for severe fibrosis of the liver. Definitive diagnosis can be established by liver biopsy. Determination of serum copper is needed when Wilson disease is the probable cause of hepatic abnormalities. Wilson disease does not cause hypogonadism, heart failure, diabetes, or arthropathy. Chronic liver disease caused by hepatitis B would not account for the heart failure, hyperpigmentation, or diabetes. Nocturnal penile tumescence and echocardiogram can confirm clinical findings but will not establish the underlying diagnosis.
A 30-year-old man is evaluated for a thyroid nodule. The patient reports that his father died from thyroid cancer and that a brother had a history of recurrent renal stones. Blood calcitonin concentration is 2000 pg/mL (normal is < 100); serum calcium and phosphate levels are normal. The patient is referred to a thyroid surgeon. Which of the following studies should also be obtained?
For the patient described, the markedly increased calcitonin level indicates the diagnosis of medullary carcinoma of the thyroid. In view of the family history, the patient most likely has multiple endocrine neoplasia (MEN) type 2A, which includes medullary carcinoma of the thyroid gland, pheochromocytoma, and parathyroid hyperplasia. Pheochromocytoma may exist without sustained hypertension, as indicated by excessive urinary catecholamines. Before thyroid surgery is performed on this patient, a pheochromocytoma must be ruled out through urinary catecholamine determinations; the presence of such a tumor might expose him to a hypertensive crisis during surgery. The serum calcium serves as a screening test for hyperparathyroidism. At surgery, the entire thyroid gland must be removed because foci of parafollicular cell hyperplasia, a premalignant lesion, may be scattered throughout the gland. Successful removal of the medullary carcinoma can be monitored with serum calcitonin levels. Medullary carcinoma of the thyroid rarely metastases to the liver, so a liver scan would be unnecessary if liver enzymes are normal. Thyroxine will be needed after surgery, but MEN type 2 is not associated with hypothyroidism. Radioactive iodine can be used to treat malignancies that arise from the follicular cells of the thyroid; parafollicular cells, however, do not take up iodine and do not respond to radioactive iodine. Hyperparathyroidism, while unlikely in this eucalcemic patient, is probably present in his brother.
A 32-year-old woman has a 3-year history of oligomenorrhea that has progressed to amenorrhea during the past year. She has observed loss of breast fullness, reduced hip measurements, acne, increased body hair, and deepening of her voice. Physical examination reveals frontal balding, clitoral hypertrophy, and a male escutcheon. Urinary free cortisol and dehydroepiandrosterone sulfate (DHEAS) are normal. Her plasma testosterone level is 6 ng/mL (normal is 0.2-0.8). Which of the following is the most likely diagnosis?
The symptoms of masculinization (eg, alopecia, deepening of voice, clitoral hypertrophy) in this patient are characteristic of an active androgen-producing tumor. Such extreme virilization is very rarely observed in polycystic ovary syndrome or in Cushing syndrome; moreover, the presence of normal cortisol and adrenal androgens (DHEA-S) plus markedly elevated plasma testosterone levels indicates an ovarian rather than adrenal cause of the findings. Arrhenoblastomas are the most common androgen-producing ovarian tumors. Their incidence is highest during the reproductive years. Composed of varying proportions of Leydig and Sertoli cells, they are generally benign. In contrast to arrhenoblastomas, granulosa-theca cell tumors produce feminization, not virilization. Dermoid cysts (benign teratomas) do not produce gonadotropins but cause symptoms by enlargement, ovarian torsion (pain) or rupture with contents spilling into the peritoneal cavity.
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