Endocrine case studies
1. A 34-year-old woman has new-onset hypertension. Her serum potassium level is 2.7 mmol/L. Initial hormone screening shows a plasma aldosterone (PA) of 55 ng/dL (normal [nl], 1–16) and a plasma renin (PR) of 0.1 ng/mL/hour (nl, 0.15–2.33). What is the probable diagnosis?
The presence of hypertension and hypokalemia suggests primary aldosteronism (Conn syndrome). The PA level is elevated, the PR is suppressed, and the PA/PR ratio is greater than 20, supporting this diagnosis. The diagnosis can be confirmed by demonstrating the failure of PA to suppress after volume expansion with intravenous saline or oral salt loading. The next step is to establish whether the cause is an aldosterone-producing adenoma or bilateral adrenal hyperplasia. Abdominal computed tomography (CT) should be performed. Because of her young age and very low serum potassium level, an aldosterone-producing adrenal adenoma is the most likely cause. The treatment for an aldosterone-producing adrenal adenoma is surgery. Spironolactone should be given to control blood pressure and to normalize the serum potassium preoperatively (see Chapter 27).
2. A 32-year-old business executive develops amenorrhea. She has not recently lost weight but states that her job is very stressful. Evaluation reveals the following laboratory results: serum estradiol = 14 pg/mL (nl, 23–145), luteinizing hormone (LH) = 1.2 mIU/mL (nl, 2–15), follicle-stimulating hormone (FSH) = 1.5 mIU/mL (nl, 2–20), prolactin = 6.2 ng/mL (nl, 2–25), thyroid-stimulating hormone (TSH) = 1.2 mU/L (nl, 0.5–5.0), and a serum pregnancy test is negative. A magnetic resonance imaging (MRI) scan of her pituitary gland is normal. What is the probable diagnosis?
The patient has secondary amenorrhea with low estradiol and gonadotropin levels. This clinical picture is most consistent with hypothalamic amenorrhea, which may occur in women who exercise excessively or have stressful jobs. The disorder results from reduced gonadotropin-releasing hormone (GnRH) pulse frequency in the hypothalamus. Treatment consists of stress management and, if menses do not resume, estrogen replacement therapy (see Chapter 47).
3. A nulliparous 48-year-old woman presents with symptoms of thyrotoxicosis. She has a modest, nontender goiter and no exophthalmos. She takes no medications and has had no recent radiology procedures. The following results are found on thyroid evaluation: free thyroxine (T4) = 3.5 ng/dL (nl, 0.8–1.8), TSH less than 0.1 mU/L, 24-hour radioactive iodine uptake (RAIU) = 1% (nl, 20%–35%), thyroglobulin = 35 ng/mL (nl, 2–20), and sedimentation rate = 10 mm/hour. What is the likely diagnosis?
The patient has clinical and biochemical thyrotoxicosis, but the RAIU is low. The differential diagnosis includes postpartum thyroiditis, silent thyroiditis, subacute thyroiditis, factitious thyrotoxicosis, and iodine-induced thyrotoxicosis. She has never been pregnant and denies medication use and recent iodine exposure. The nontender gland, elevated thyroglobulin, and normal sedimentation rate are most consistent with silent thyroiditis. A transient (1–3 months) thyrotoxic phase followed by a transient (1–3 months) hypothyroid phase is expected before the condition resolves; 20% of patients, however, remain hypothyroid. If symptomatic, the thyrotoxic phase is best treated with beta-blockers, and the hypothyroid phase can be managed, if necessary, with levothyroxine (see Chapters 33 and 35).
4. A 38-year-old man has coronary artery disease, xanthomas of the Achilles tendons, and the following serum lipid profile: cholesterol = 482 mg/dL, triglyceride (TG) = 125 mg/dL, high-density lipoprotein (HDL) cholesterol = 42 mg/dL, and low-density lipoprotein (LDL) cholesterol = 415 mg/dL. What is the probable diagnosis?
Significant elevations of total cholesterol and LDL cholesterol, normal TG, tendon xanthomas, and premature coronary artery disease are most consistent with a diagnosis of heterozygous familial hypercholesterolemia. This disorder is usually the result of deficient or abnormal LDL receptors or an abnormal apoprotein B-100 molecule. Aggressive lipid lowering with a combination of statins, ezetimibe, bile acid resins, and niacin is needed. In many cases, LDL apheresis is also indicated (see Chapter 6).
5. A 28-year-old man presents because of infertility. He is found to have small, firm testes and gynecomastia. Laboratory testing shows the following abnormalities: testosterone = 206 ng/dL (nl, 300–1000), LH = 88 mIU/mL (nl, 2–12), and FSH = 95 mIU/mL (nl, 2–12). What is the likely diagnosis?
The patient has hypergonadotropic hypogonadism with small firm testes and gynecomastia, which is most consistent with a diagnosis of Klinefelter syndrome. Such patients usually have a 47XXY karyotype. Androgen replacement therapy is the treatment of choice (see Chapters 43 and 44).
6. A 38-year-old nurse presents in a stuporous state; the blood glucose level is 14 mg/dL. Additional blood is drawn, and the patient is quickly resuscitated with intravenous glucose. Further testing on the saved serum reveals the following: serum insulin = 45 μU/mL (nl, <22), C-peptide = 4.2 ng/mL (nl, 0.5–2.0), and proinsulin = 7 pmol/L (nl, <5). A sulfonylurea screen is negative. What is the probable diagnosis?
The patient has hyperinsulinemic hypoglycemia. The differential diagnosis includes insulinoma, surreptitious insulin injection, and oral sulfonylurea ingestion. The elevated serum C-peptide and proinsulin levels are most consistent with an insulinoma. After an appropriate localizing procedure, surgical removal is the treatment of choice (see Chapter 53).
7. A 28-year-old woman develops amenorrhea. She has type 1 diabetes mellitus. Further testing reveals the following serum hormone values: estradiol = 15 pg/mL (nl, 23–145), LH = 78 mIU/mL (nl, 2–15), FSH = 92 mIU/mL (nl, 2–20), prolactin = 12 ng/mL (nl, 2–25), TSH = 1.1 mU/L; a pregnancy test is negative. What is the most likely diagnosis?
The patient has secondary amenorrhea with low estradiol and elevated gonadotropin levels. In a patient with another autoimmune disease (type 1 diabetes mellitus), the most likely diagnosis is premature ovarian failure resulting from autoimmune ovarian destruction. Hormone replacement therapy is the treatment of choice (see Chapter 47).
8. A 34-year-old woman presents with galactorrhea, amenorrhea, headaches, fatigue, and weight gain. Laboratory evaluation reveals the following: prolactin = 58 ng/mL (nl, 2–25), free T4 = 0.2 ng/dL (nl, 0.8–1.8), and TSH greater than 60 mU/L (nl, 0.5–5.0). She has an enlarged pituitary gland on MRI scan. What is the probable diagnosis?
The patient has moderately increased serum prolactin levels, pituitary enlargement, and severe primary hypothyroidism. Her entire clinical picture is most likely explained solely by the hypothyroidism, which is well known to cause secondary hypersecretion of prolactin and pituitary enlargement from thyrotroph hyperplasia. All abnormalities should resolve after adequate thyroid hormone replacement is established (see Chapters 20 and 47).
9. A 6-year-old girl has recently developed breast enlargement and some pubic hair. She has not complained of headaches and has had good health otherwise. Her older sister entered puberty at approximately 8 years of age. Her height is at the 90th percentile for her age, and her physical examination reveals Tanner stage III breast development and stage II pubic hair growth. Abdominal and pelvic examinations are normal. Laboratory tests show the following results: LH = 7 mIU/mL (nl, 2–15), FSH = 8 mIU/mL (nl, 2–20), prolactin = 6 ng/mL (nl, 2–25), TSH = 1.9 mU/L (nl, 0.5–5.0), and a normal pituitary MRI scan. Her bone age is 1.8 years ahead of the chronologic age. What is the probable diagnosis?
The patient has gonadotropin-dependent true precocious puberty. The etiology includes pituitary and hypothalamic tumors, but most cases in girls are idiopathic. The normal pituitary MRI points to a diagnosis of idiopathic precocious puberty. A long-acting GnRH analog should successfully arrest her premature development and allow her to enter puberty at a later, more appropriate time (see Chapter 43).
10. A 19-year-old man presents with excessive thirst and urination. Laboratory evaluation shows the following: serum glucose = 88 mg/dL, serum sodium = 146 mmol/L, serum osmolality = 298 mOsm/kg, and urine volume = 8800 mL/24 hour. A water deprivation test is performed, and it shows a urine osmolality of 90 mOsm/kg with no response to water deprivation and an increase in urine osmolality to 180 mOsm/kg after the administration of vasopressin. What is the likely diagnosis?
The patient has polyuria and polydipsia with maximally dilute urine. The differential diagnosis includes central diabetes insipidus, nephrogenic diabetes insipidus, and primary polydipsia. The lack of response to water deprivation and the more than 50% increase in urine osmolality after administration of vasopressin are most consistent with central diabetes insipidus. This may be caused by inflammatory or mass lesions in the hypothalamus but is often idiopathic. An MRI scan of the pituitary-hypothalamic region should be performed. The treatment of choice is intranasal or oral desmopressin (see Chapters 18 and 24).
11. A 25-year-old woman presents with a cushingoid appearance. The results of hormone testing are as follows: 24-hour urine cortisol = 318 μg (nl, 20–90), morning serum cortisol = 28 μg/dL (nl, 5–25), and morning plasma adrenocorticotropic hormone (ACTH) = 65 pg/mL (nl, 10–80). After an 8-mg oral bedtime dose of dexamethasone, the morning serum cortisol = 3 μg/dL. What is the probable diagnosis?
Cushingoid features and significantly elevated urinary cortisol excretion confirm the diagnosis of Cushing syndrome. The cause is usually an ACTH-secreting pituitary adenoma (65%–80%), ectopic production of ACTH (10%–15%), or a cortisol-producing adrenal adenoma (10%–15%). The normal plasma level of ACTH, which is inappropriate for the elevated serum cortisol level, and suppression of serum cortisol with high-dose dexamethasone are most consistent with a pituitary adenoma (Cushing’s disease). This should be confirmed with an MRI scan of the pituitary gland and possibly inferior petrosal sinus sampling. Transsphenoidal surgical removal is the treatment of choice (see Chapter 23).
12. An 8-year-old boy with known adrenal insufficiency complains of paresthesias of the lips, hands, and feet and intermittent muscle cramps. He has positive Chvostek’s and Trousseau’s signs on examination. Results of blood testing are as follows: calcium = 6.2 mg/dL (nl, 8.5–10.2), phosphorus = 5.8 mg/dL (nl, 2.5–4.5), intact parathyroid hormone (PTH) = 3 pg/mL (nl, 10–65), and 25-hydroxyvitamin D = 42 ng/mL (nl, 30–100). What is the most likely diagnosis?
Hypocalcemia, hyperphosphatemia, and a low serum PTH level are diagnostic of primary hypoparathyroidism. This disorder, which is often autoimmune, may occur in association with adrenal insufficiency as part of the autoimmune polyendocrine syndrome type 1 (APS 1). Hypoparathyroidism must be treated with both calcium and calcitriol supplementation. Calcitriol is necessary because PTH, the missing hormone, is necessary for normal renal conversion of 25-hydroxyvitamin D into 1,25-dihydroxyvitamin D, the active vitamin D metabolite that is necessary for normal intestinal calcium absorption. A thiazide diuretic is also often helpful to increase the serum calcium further and to reduce treatment-induced hypercalciuria (see Chapters 16 and 52).
13. A 52-year-old man has a personal and family history of early coronary artery disease, minimal alcohol consumption, and no xanthomas on examination. He has the following results on serum testing: cholesterol = 328 mg/dL, TG = 322 mg/dL, HDL = 35 mg/dL, LDL = 229 mg/dL, apoprotein B = 178 mg/dL (nl, 60–130), apoprotein E phenotype = E3/E3, TSH = 2.1 mU/L (nl, 0.1–4.5), and glucose = 85 mg/dL. What is the probable diagnosis?
The patient has elevations of both serum cholesterol and TG and no detected disorders that cause secondary dyslipidemia. The differential diagnosis includes familial combined hyperlipidemia and familial dysbetalipoproteinemia. The elevated level of apoprotein B and the normal apoprotein E phenotype are most consistent with familial combined hyperlipidemia. The top treatment priority is LDL reduction with a statin. After LDL cholesterol is lower than the National Cholesterol Education Program (NCEP) goal, persistent TG elevations should be addressed with the possible addition of a fibrate, niacin, or fish oils (see Chapter 6).
14. A 58-year-old man has recently developed diabetes mellitus, weight loss, and a skin rash that is most prominent on the buttocks; a dermatologist diagnoses this as necrolytic migratory erythema. What is the probable underlying diagnosis?
Diabetes mellitus, weight loss, and necrolytic migratory erythema are virtually diagnostic of a glucagon-secreting pancreatic endocrine tumor (glucagonoma). The diagnosis can be confirmed by finding an elevated serum level of glucagon. After appropriate localizing procedures, surgery is the treatment of choice, if possible. Chemotherapy should be considered for unresectable malignant tumors or tumor remnants (see Chapter 53).
15. A 29-year-old woman has asymptomatic hypercalcemia. Her mother and a sister also have hypercalcemia and have had failed neck explorations for presumed parathyroid tumors. Further testing results: serum calcium = 11.0 mg/dL (nl, 8.5–10.2), phosphorus = 3.0 mg/dL (nl, 2.4–4.5), creatinine = 0.9 mg/dL, intact PTH = 66 pg/mL (nl, 10–65), 25-hydroxyvitamin D = 42 ng/mL (nl, 30–100), 24-hour urine calcium = 13 mg (nl, 100–300), and creatinine = 1100 mg. What is the probable diagnosis?
Most patients with hypercalcemia and a mildly elevated serum PTH level have primary hyperparathyroidism. However, in this case, the very low urinary calcium excretion and family history of unsuccessful parathyroid surgical procedures point to a likely diagnosis of familial hypocalciuric hypercalcemia. The diagnosis is confirmed by finding a calcium/creatinine clearance ratio (urine calcium × serum creatinine/serum calcium × urine creatinine) of less than 0.01. This autosomal dominant disorder results from a heterozygous inactivating mutation in the gene that encodes the calcium sensor receptor. The mutant sensor receptors, present in parathyroid and renal tubular cells, have a raised threshold for calcium recognition. The result is a physiologic equilibrium, in which hypercalcemia coexists with mild elevations of PTH and low urinary calcium excretion. The disorder causes no morbidity and does not require treatment (see Chapters 13 and 14).
16. A 39-year-old human immunodeficiency virus (HIV)-positive man with Pneumocystis carinii pneumonia has the following serum thyroid hormone values: free T4 = 0.8 ng/dL (nl, 0.8–1.8), total triiodothyronine (T3) = 22 ng/dL (nl, 90–200), and TSH = 0.5 mU/L (nl, 0.5–5.0). What is the most likely endocrine diagnosis?
The very low T3, low normal free T4, and low normal TSH are most consistent with the euthyroid sick syndrome. This is not a primary thyroid disorder but is instead a set of circulating thyroid hormone abnormalities that occur in the presence of nonthyroidal illnesses; it corrects when the underlying illness resolves. Treatment of the condition with thyroid hormone administration is not currently recommended, although this remains controversial (see Chapter 39).
17. An 18-year-old woman has not yet begun menstruating. She has a height of 56 inches, a small uterus, and no breast development. The results of hormone tests are as follows: estradiol = 8 pg/mL (nl, 23–145), LH = 105 mIU/mL (nl, 2–15), FSH = 120 mIU/mL (nl, 2–20), prolactin = 14 ng/mL (nl, 2–15), and TSH = 1.8 mU/L (nl, 0.5–5.0). What is the probable diagnosis?
Primary amenorrhea, short stature, low serum estradiol, and elevated gonadotropins are most consistent with a diagnosis of Turner syndrome. This disorder, characterized by ovarian dysgenesis, is associated with a 45XO karyotype. These patients should be given hormone replacement therapy with estrogen and progesterone. Growth hormone (GH) therapy should be considered because it improves longitudinal growth and final height (see Chapters 43 and 47).
18. A 62-year-old woman presents for evaluation of recent nephrolithiasis and low back pain. Her estimated calcium intake is 800 mg/day, and she takes no vitamins. Her physical examination is unremarkable. Spinal radiographs reveal a compression fracture of the second lumbar vertebra (L2). Laboratory evaluation shows the following: serum calcium = 13.0 mg/dL (nl, 8.5–10.5), phosphorus = 2.3 mg/dL (nl, 2.5–4.5), albumin = 4.4 g/dL (nl, 3.2–5.5), intact PTH = 72 pg/mL (nl, 11–54), and 24-hour urine calcium = 312 mg (nl, 100–300). What is the most likely diagnosis?
Hypercalcemia, hypophosphatemia, and elevated serum PTH levels are characteristic of primary hyperparathyroidism. Hyperparathyroidism is usually the result of a solitary parathyroid adenoma; familial cases and those associated with multiple endocrine neoplasia (MEN) syndromes more often have four-gland hyperplasia. Surgical indications include serum calcium levels greater than 1 mg/dL above the normal range, renal impairment, osteoporosis, age less than 50 years, or symptoms related to hyperparathyroidism. Observation alone or bisphosphonate therapy may be appropriate for patients with mild, asymptomatic disease or only mild bone loss. This patient should be referred for parathyroid surgery (see Chapter 14).
19. A 32-year-old woman presents with the recent onset of fatigue, palpitations, profuse sweating, and emotional lability. She gave birth to her second child 8 weeks ago. Her pulse is 100/minute, and she has mild lid retraction, a fine hand tremor, and a slightly enlarged, nontender thyroid gland. She is not breast-feeding her child. Laboratory tests are as follows: TSH less than 0.03 mU/L (nl, 0.5–5.0), free T4 = 3.8 ng/dL (nl, 0.8–1.8), and RAIU less than 1% at 4 and 24 hours. What is the probable diagnosis?
Postpartum thyrotoxicosis is most often secondary to Graves’ disease or postpartum thyroiditis. The RAIU will distinguish the two; it is high in Graves’ disease and low in postpartum thyroiditis. RAIU is contraindicated in patients who are breast-feeding; in those cases, measurement of TSH receptor antibodies (TRAb) is often useful, being positive in Graves’ disease and negative in postpartum thyroiditis. This patient has postpartum thyroiditis, a condition caused by lymphocytic inflammation with leakage of thyroid hormone from the inflamed gland. There is often a thyrotoxic phase (lasting 1–3 months) followed by a hypothyroid phase (lasting 1–3 months) and eventual return to euthyroidism, although nearly 20% remain permanently hypothyroid. Treatment consists of beta-blockers, if necessary, for symptom control in the thyrotoxic phase, and levothyroxine, if necessary, for symptom control in the hypothyroid phase and for those who remain permanently hypothyroid (see Chapters 33 and 35).
20. A 70-year-old man complains of a 1-year history of weakness, weight loss, and hand tremors. He has been treated with amiodarone for nearly 3 years for paroxysmal atrial flutter. Laboratory tests show the following: TSH less than 0.01 mU/L (nl, 0.5–5.0), free T4 = 3.35 ng/dL (nl, 0.8–1.8), and RAIU = 2.7% at 6 hours and 4.1% at 24 hours. Thyroid scan showed patchy tracer uptake. What is the likely diagnosis?
This man has amiodarone-induced thyrotoxicosis (AIT). The condition occurs in up to 10% of patients using amiodarone, which has a very high iodine content. There are two subtypes: type 1 AIT results from iodine overload and occurs mainly in patients with underlying goiters; type 2 AIT results from amiodarone-induced thyroid follicular damage. Both are associated with a low RAIU. No tests reliably distinguish the two subtypes, although an underlying goiter and detectable RAIU are more common in type 1 AIT. Type 1 AIT is best treated with methimazole, whereas type 2 AIT responds better to steroid therapy. Difficult cases may require both these medications, dialysis, plasmapheresis, or thyroidectomy (see Chapter 33).
21. A 20-year-old man presents for failure to enter puberty. He has small, soft testes, no gynecomastia, normal visual fields, and decreased sense of smell. Laboratory evaluation is as follows: serum testosterone = 70 ng/dL (nl, 300–1000), LH = 2.0 mIU/mL (nl, 2–12), FSH = 1.6 mIU/mL (nl, 2–12), prolactin = 7 ng/mL (nl, 2–20), and TSH = 0.9 mU/L (nl, 0.5–5.0). An MRI scan of the pituitary gland is normal. What is the probable diagnosis?
This picture is most consistent with idiopathic hypogonadotropic hypogonadism, also known as Kallmann syndrome. This disorder is caused by a deficiency of GnRH, resulting from failure of fetal migration of the GnRH-secreting neurons from the olfactory placode to the hypothalamus. Mutations of the Kal gene have been detected in some patients. Maldevelopment of the olfactory lobe causes the associated anosmia. Androgen therapy is indicated to promote appropriate masculinization. When desired, these patients can also become fertile by receiving treatment with GnRH or gonadotropin preparations (see Chapters 43 and 44).
22. A 32-year-old man complains of impotence and retroorbital headaches intermittently for the past year. He is adopted and does not know his natural family history. He has bitemporal visual field loss, but his examination is otherwise normal. Laboratory tests reveal the following: serum calcium = 11.8 mg/dL (nl, 8.5–10.5), phosphorus = 2.5 mg/dL (nl, 2.5–4.5), albumin = 4.8 g/dL (nl, 3.2–5.5), intact PTH = 58 pg/mL (nl, 11–54), and prolactin = 2650 ng/mL (nl, 0–20). What is the likely diagnosis?
This patient has a prolactinoma, manifested by impotence, headaches, bitemporal hemianopsia, and a significantly elevated serum prolactin level. Hypercalcemia with an elevated serum PTH level indicates that he also has hyperparathyroidism. The MEN type 1 (MEN-1) syndrome, which consists of hyperparathyroidism, pituitary tumors, and pancreatic endocrine tumors, results from an inherited mutation in the Menin gene. This patient should be screened for gastrinoma by ordering a fasting serum gastrin and for insulinoma by measuring serum glucose, insulin, C-peptide, proinsulin, and beta-hydroxybutyrate following an overnight fast or during a prolonged supervised fast. After pituitary imaging studies, he should be treated with a dopamine agonist, transsphenoidal surgery, or both, and subsequently with parathyroid surgery (see Chapters 20 and 51).
23. A 52-year-old woman complains of a 1-year history of progressive fatigue, puffy eyes, dry skin, and mild weight gain. She had acromegaly treated with transsphenoidal surgery and radiation therapy 10 years ago. Physical examination shows normal visual fields, mild periorbital edema, and dry skin. Laboratory testing reveals the following: GH = 1.2 ng/mL (nl, < 2.0), insulin-like growth factor-I (IGF-I) = 258 ng/mL (nl, 182–380), TSH = 0.2 mU/L (nl, 0.5–5.0), and free T4 = 0.5 ng/dL (nl, 0.8–1.8). What is the most likely cause of this patient’s symptoms?
She has central hypothyroidism resulting from pituitary damage from the combined effects of surgery and radiation treatment of her pituitary tumor 10 years earlier. Such a lengthy delay in the development of this condition is not uncommon. The diagnosis of central hypothyroidism is based on the presence of symptoms of thyroid hormone deficiency, a low serum free T4, and a low or low-normal serum TSH. Treatment consists of levothyroxine replacement in doses sufficient to relieve symptoms and to maintain the serum free T4 level in the midnormal or upper-normal range. Because TSH secretion is impaired, the serum TSH level cannot be used to monitor this patient’s response to therapy. Assessment of her pituitary-adrenal axis is also indicated (see Chapters 18 and 34).
24. A 32-year-old woman complains of deep pain in both thighs. She was diagnosed as having type 1 diabetes mellitus at age 20 years. She currently has two to three bowel movements each day. Her menses are regular. Her diet is well balanced with adequate calcium intake, and she takes a multivitamin. Physical examination is normal. Laboratory studies show the following: serum calcium = 8.2 mg/dL (nl, 8.5–10.5), phosphorus = 2.3 mg/dL (nl, 2.5–4.5), alkaline phosphatase = 312 U/L (nl, 25–125), PTH = 155 pg/mL (nl, 11–54), and 25-hydroxyvitamin D = 7 ng/mL (nl, 30–100). Explain the findings in this patient, and suggest a probable underlying diagnosis.
Her biochemical profile of hypocalcemia, hypophosphatemia, elevated alkaline phosphatase, and significant secondary hyperparathyroidism suggests vitamin D deficiency, which is confirmed by the low serum 25-hydroxyvitamin D level. The elevated serum alkaline phosphatase suggests that the vitamin D deficiency has been sufficiently severe and prolonged to result in osteomalacia. Lactose intolerance can cause chronic diarrhea but seldom results in vitamin D and calcium malabsorption. Celiac disease (gluten sensitive enteropathy), which occurs with increased frequency in patients with type 1 diabetes mellitus, should be suspected. The diagnosis can be confirmed by the measurement of tissue transglutaminase antibodies or by a small bowel biopsy. The treatment is elimination of gluten (wheat, rye, barley, oats) from the diet and supplementation with calcium and vitamin D (see Chapter 11).
25. A 42-year-old man presents for evaluation of a skin rash that has recently developed. He has known type 2 diabetes mellitus. He drinks two to three alcoholic beverages several nights each week. Physical examination shows eruptive xanthomas (red papules with golden crowns) all over his body, most prominently on the buttocks, thighs, and forearms. Laboratory studies reveal the following: glucose = 310 mg/dL, hemoglobin A1C (HbA1C) = 12.9%, cholesterol = 1082 mg/dL, and TG = 8900 mg/dL. Discuss the cause and treatment of this lipid disorder
The patient has severely elevated serum TG. This condition usually results from combining a secondary cause of TG elevation (uncontrolled diabetes mellitus, excess alcohol use) with an inherited TG disorder (familial hypertriglyceridemia or familial combined hyperlipidemia). His LDL cholesterol cannot be assessed until the serum TG levels are less than 400 mg/dL. Because he is at high risk of developing acute pancreatitis, the priority is to lower his serum TG level quickly to less than 1000 mg/dL. This goal can be achieved most effectively with a temporary very low-fat (<5% fat) diet, blood glucose control, and discontinuation of alcohol. TG levels will fall by about 20% a day on this regimen. A fibrate or fish oil (or both) should then be added, and he should be switched to an American Heart Association diet. Diabetes control must be continued and further alcohol intake discouraged (see Chapter 6).
26. A 26-year-old woman requests to be tested for a type of thyroid cancer that has recently been found in her mother and two of five siblings. She notes that she has had intermittent headaches and palpitations for the past year. Her blood pressure is 164/102. She has a 1-cm, left-sided thyroid nodule without associated lymphadenopathy. Laboratory testing shows the following results: serum calcium = 11.2 mg/dL (nl, 8.5–10.5), phosphorus = 2.4 mg/dL (nl, 2.5–4.5), albumin = 4.5 g/dL (nl, 3.2–5.5), intact PTH = 55 pg/mL (nl, 11–54), calcitonin = 480 pg/mL (nl, 0–20), and 24-hour urine catecholamines = 1225 μg (nl, 0–200). Discuss her diagnosis and management.
The thyroid nodule, elevated serum calcitonin, and family history make medullary carcinoma of the thyroid (MCT) likely. Hypertension, headaches, palpitations, and high urinary catecholamines indicate a probable pheochromocytoma. She also has hyperparathyroidism. MEN type 2A (MEN-2A) consists of MCT, pheochromocytoma, and hyperparathyroidism. It is an autosomal dominant syndrome that results from a germline mutation in the Ret gene. After alpha-blocker initiation and blood pressure control, treatment should consist of removal of the pheochromocytoma(s), followed by later removal of the abnormal thyroid and parathyroid glands. Screening at-risk family members for the Ret/MCT oncogene should also be performed (see Chapters 37 and 51).
27. A 68-year-old man complains of a 10-year history of progressive pain in the shins, knees, and left arm. He also notes progressive hearing loss. Physical examination reveals tenderness above the left elbow and enlarged, bowed shins. Bone scan shows intense uptake in both tibias and the left humerus. Skeletal radiographs show enlargement with multiple focal lytic and sclerotic areas in the tibias and the distal left humerus. Laboratory evaluation reveals serum calcium = 9.8 mg/dL (nl, 8.5–10.5) and alkaline phosphatase = 966 U/L (nl, 25–125). What is the probable diagnosis?
Bone pain and deformity, reduced hearing, and markedly elevated serum alkaline phosphatase levels suggest a diagnosis of Paget’s disease. Intense radioisotope uptake on bone scanning supports this diagnosis, and the characteristic findings on skeletal radiographs confirm it. Treatment options include analgesics, intravenous bisphosphonates (zoledronic acid preferred), subcutaneous denosumab, and calcitonin, all of which may control but will not cure the disease (see Chapter 12).
28. A 19-year-old man has experienced fatigue, muscle weakness, and dizziness for the past 3 weeks. This morning he fainted when he went outdoors to exercise. His blood pressure is 95/60 mm Hg, and his pulse is 110. His skin is cool, dry, and tanned. His thyroid feels normal. Laboratory testing shows the following: hematocrit = 36%, glucose = 62 mg/dL, sodium = 120 mmol/L, potassium = 6.7 mmol/L, creatinine = 1.4 mg/dL, and blood urea nitrogen (BUN) = 36 mg/dL. What endocrine disorder should be considered and evaluated?
Hyponatremia with hyperkalemia always suggests primary adrenal insufficiency (Addison’s disease). Fatigue, weakness, hypotension, tanned skin, anemia, azotemia, and hypoglycemia are also consistent with this diagnosis. The most common cause is autoimmune destruction of the adrenal glands. The diagnosis is made by a basal serum cortisol level lower than 3 μg/dL or by a cosyntropin stimulation test that shows a low basal serum cortisol level that fails to increase after ACTH administration. During an adrenal crisis, however, one does not have time to wait for the test results. When this diagnosis is suspected, one should draw blood for a serum cortisol measurement and then start treatment with intravenous fluids and glucocorticoids (hydrocortisone, 100 mg every 6–8 hours). Precipitating conditions should be actively sought and treated. After the patient is stable, he can be switched to oral hydrocortisone and fludrocortisone for chronic maintenance (see Chapter 30).
