Metabolic And Growth Disorders - USMLE Step 1

1. A tumor secreting an excess of which of the following hormones best explains this triad of symptoms?
   Answer: Somatostatin The classic triad for a somatostatinoma is diabetes mellitus (due to inhibition of insulin and glucagon secretion), steatorrhea (due to inhibition of pancreatic exocrine secretions and cholecystokinin), and cholelithiasis (due to inhibition of gallbladder motility). Somatostatin is a potent inhibitor of many gastrointestinal and pancreatic hormones, leading to this constellation of findings.
2. The pathologic process responsible for this patient's condition occurs before which of the following events?
   Answer: Epiphyseal plate fusion This patient has gigantism, which is caused by excessive growth hormone (GH) secretion from a pituitary adenoma occurring before the fusion of the long bone epiphyseal plates. The excess GH and its mediator, IGF-1, stimulate excessive linear bone growth, resulting in tall stature. If the same condition occurs after epiphyseal fusion in adulthood, it is called acromegaly, which causes growth of acral parts but not an increase in height.
3. This patient's condition is most likely caused by a tumor secreting which of the following hormones?
   Answer: Glucagon This patient's constellation of symptoms, including diabetes mellitus, weight loss, diarrhea, and the characteristic skin rash known as necrolytic migratory erythema, is classic for glucagonoma syndrome. This is caused by a glucagon-secreting tumor of the pancreatic alpha cells. The diagnosis is confirmed by a markedly elevated serum glucagon level.
4. This patient's symptoms are most likely caused by a pancreatic tumor that secretes which of the following substances?
   Answer: Vasoactive intestinal peptide (VIP) This patient has Verner-Morrison syndrome, or WDHA syndrome (Watery Diarrhea, Hypokalemia, Achlorhydria), which is caused by a VIPoma, a rare neuroendocrine tumor of the pancreas that secretes vasoactive intestinal peptide (VIP). VIP stimulates intestinal water and electrolyte secretion, leading to voluminous secretory diarrhea, and inhibits gastric acid secretion, causing achlorhydria. The massive loss of potassium in the stool results in profound hypokalemia.
5. This patient's condition is associated with an increased risk of which of the following cardiovascular abnormalities?
   Answer: Coarctation of the aorta This patient's clinical presentation is classic for Turner syndrome (45,X karyotype). In addition to short stature and gonadal dysgenesis, patients with Turner syndrome have a significantly increased risk of congenital cardiovascular abnormalities. The most common are bicuspid aortic valve and coarctation of the aorta.
6. This patient's clinical course is best explained by a deficiency of which of the following enzymes?
   Answer: 5-alpha-reductase This patient has 5-alpha-reductase deficiency, an autosomal recessive disorder affecting 46,XY individuals. This enzyme is responsible for converting testosterone to the more potent dihydrotestosterone (DHT). DHT is required for the development of the external male genitalia in utero. Its deficiency leads to ambiguous or female-like external genitalia at birth. At puberty, the surge in testosterone can induce virilization, causing phallic growth, voice deepening, and muscle development.
7. Dysfunction in which of the following glands is the most likely cause of this patient's condition?
   Answer: Anterior pituitary The patient's presentation of short stature, delayed bone age, low IGF-1, and a blunted response to GH stimulation testing is classic for growth hormone deficiency. Growth hormone is produced and secreted by the somatotroph cells of the anterior pituitary. Therefore, dysfunction of the anterior pituitary is the most likely cause.
8. A defect in which of the following is the most likely cause of this patient's condition?
   Answer: Growth hormone receptor This patient presents with Laron syndrome, a form of dwarfism characterized by growth hormone insensitivity. It is caused by a defect in the growth hormone receptor. The anterior pituitary produces adequate or even excessive GH, but the target tissues (primarily the liver) cannot respond to it. This leads to a failure to produce IGF-1, resulting in short stature despite high GH levels. The lack of negative feedback from IGF-1 on the pituitary leads to the elevated GH.
9. A deficiency of which of the following enzymes is the most likely cause of this infant's condition?
   Answer: 21-hydroxylase This infant presents with salt-wasting congenital adrenal hyperplasia (CAH), which is most commonly caused by 21-hydroxylase deficiency. This enzyme defect impairs the synthesis of both cortisol and aldosterone. The lack of aldosterone leads to salt wasting (hyponatremia, hyperkalemia) and hypotension. The lack of cortisol leads to hypoglycemia and increased ACTH secretion. The precursors proximal to the block are shunted towards androgen synthesis, causing virilization (ambiguous genitalia) in female infants.
10. Which of the following sets of laboratory findings would be most consistent with an insulinoma?
    Answer: Low glucose, high insulin, high C-peptide The diagnosis of an insulinoma, a tumor of pancreatic beta cells, is confirmed by documenting Whipple's triad (symptoms of hypoglycemia, low plasma glucose, and relief of symptoms with glucose administration) along with inappropriately high insulin levels. During hypoglycemia, normal beta cells would be suppressed. An insulinoma autonomously secretes insulin, leading to high insulin levels despite low glucose. Because the insulin is endogenous, C-peptide (which is cleaved from proinsulin during insulin synthesis) will also be elevated. Exogenous insulin administration would cause high insulin but low C-peptide.
11. Overproduction of which hormone is the most likely cause of this patient's condition?
    Answer: Gastrin The presentation of multiple, refractory peptic ulcers, especially in atypical locations like the jejunum, is highly suggestive of Zollinger-Ellison syndrome (ZES). ZES is caused by a gastrin-secreting tumor (gastrinoma), most commonly located in the pancreas or duodenum. The excessive gastrin stimulates parietal cells to secrete massive amounts of gastric acid, leading to severe peptic ulcer disease and inactivation of pancreatic enzymes (causing diarrhea/steatorrhea).
12. This patient's condition is most likely caused by which of the following mechanisms?
    Answer: Premature activation of the hypothalamic-pituitary-gonadal axis This patient has central precocious puberty, also known as gonadotropin-dependent precocious puberty. The key diagnostic finding is the pubertal response (a significant rise in LH and FSH) to a GnRH stimulation test. This indicates that the hypothalamic-pituitary-gonadal (HPG) axis has been prematurely activated, leading to the early onset of puberty. It is often idiopathic in girls but can be caused by CNS lesions.
13. The development of female external genitalia in this patient is due to the failure of which of the following embryological processes?
    Answer: Virilization of the urogenital sinus and genital tubercle This patient has androgen insensitivity syndrome (AIS). The 46,XY karyotype and presence of testes indicate genetic maleness. The testes produce both anti-Müllerian hormone (causing Müllerian duct regression) and testosterone. However, due to defective androgen receptors, testosterone and its metabolite DHT cannot exert their effects. This leads to a failure of virilization of the urogenital sinus, genital tubercle, and labioscrotal folds, which then develop along the default female pathway, resulting in female external genitalia.
14. This patient's tumor is most likely derived from which of the following embryologic structures?
    Answer: Rathke's pouch The clinical and radiological findings—a child with a suprasellar calcified mass causing visual field defects and endocrine dysfunction (growth failure)—are classic for a craniopharyngioma. These benign but locally invasive tumors are derived from remnants of Rathke's pouch, the embryologic precursor of the anterior pituitary gland.
15. This patient's lack of smell is most likely related to a developmental failure of which of the following?
    Answer: Migration of GnRH-releasing neurons The combination of hypogonadotropic hypogonadism (delayed puberty with low LH and FSH) and anosmia (lack of smell) is characteristic of Kallmann syndrome. This genetic disorder results from the failed migration of GnRH-releasing neurons from their origin in the olfactory placode to their final destination in the hypothalamus during embryonic development. This leads to a deficiency of GnRH and subsequent failure to initiate puberty.
16. This patient should be screened for a mutation in which of the following genes?
    Answer: RET The patient's triad of medullary thyroid carcinoma (MTC), pheochromocytoma (suggested by paroxysmal hypertension and elevated metanephrines), and primary hyperparathyroidism (suggested by elevated calcium) is characteristic of multiple endocrine neoplasia, type 2A (MEN2A). MEN2A and MEN2B are caused by germline activating mutations in the RET proto-oncogene.
17. This patient's condition is most commonly caused by which of the following?
    Answer: Pituitary adenoma The clinical presentation of enlarged extremities, coarse facial features, and elevated IGF-1 is characteristic of acromegaly, which results from excessive growth hormone (GH) secretion after the closure of epiphyseal plates. The most common cause (in >95% of cases) is a GH-secreting pituitary adenoma. The headaches and visual changes are due to the mass effect of the adenoma on surrounding structures like the optic chiasm.
18. In addition to medullary thyroid carcinoma and pheochromocytoma, which of the following is a characteristic feature of this patient's syndrome?
    Answer: Mucosal neuromas This patient's presentation with medullary thyroid carcinoma, pheochromocytoma, marfanoid habitus (tall, thin), and nodules on the lips and tongue is classic for multiple endocrine neoplasia, type 2B (MEN2B). The characteristic features that distinguish MEN2B from MEN2A are the presence of mucosal neuromas (on lips, tongue, conjunctivae), marfanoid body habitus, and the absence of hyperparathyroidism.
19. This patient's constellation of findings is most consistent with which of the following syndromes?
    Answer: Multiple endocrine neoplasia, type 1 This patient has multiple endocrine neoplasia, type 1 (MEN1), an autosomal dominant disorder characterized by the '3 Ps': Parathyroid tumors (hyperparathyroidism, causing hypercalcemia and kidney stones), Pancreatic endocrine tumors (e.g., gastrinoma causing Zollinger-Ellison syndrome), and Pituitary adenomas. The patient's gastrinoma and hyperparathyroidism, along with a positive family history, strongly suggest MEN1.
20. Which of the following karyotypes is most likely to be found in this patient?
    Answer: 47,XXY The clinical features described—tall stature with eunuchoid proportions, gynecomastia, and small, firm testes—are characteristic of Klinefelter syndrome. This genetic disorder is caused by the presence of an extra X chromosome in males, resulting in a 47,XXY karyotype. The condition leads to primary hypogonadism with testicular atrophy, low testosterone, and elevated gonadotropins (hypergonadotropic hypogonadism).

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