Endocrine Flashcards
What enzyme-deficiency is this?
11β-Hydroxylase deficiency is suggested by the constellation of hypertension, masculinization, and hypokalemia.
How is 11β-Hydroxylase deficiency differentiated from a more common, but similar, enzyme deficiency?
21β-Hydroxylase deficiency presents with hypotension and hyperkalemia. Both deficiencies present with masculinization of the external genitalia. A review of adrenal steroid synthesis is shown in Figure 6-1.
How does 11β-Hydroxylase deficiency result in hypertension?
11β-Hydroxylase converts 11-deoxycorticosterone into corticosterone, and 11-deoxycortisol into cortisol. 11β-Hydroxylase deficiency causes a lack of cortisol and aldosterone. However, the precursor 11-deoxycortisone is a weak mineralocorticoid and causes hypertension.
What is the appropriate treatment for 11β-Hydroxylase deficiency?
Dexamethasone or hydrocortisone can be used to replace the missing corticosteroid. The lowest effective dose should be used to avoid the Cushingoid adverse effects of glucocorticoids, including bone demineralization and growth retardation.
What is the mode of inheritance of 11β-Hydroxylase deficiency?
Inheritance is autosomal recessive, with mutations in the CYP11B1 gene. All of the congenital adrenal hyperplasias are inherited in an autosomal recessive manner.
What is the most likely diagnosis? What enzyme deficiency is responsible for this condition?
The patient’s ambiguous external genitalia (masculinization) and hypotension suggest congenital adrenal hyperplasia. These signs are caused by lack of cortisol and aldosterone.
The defective enzyme is 21β-hydroxylase, an enzyme in the pathway that converts cholesterol into aldosterone and cortisol (Figure 6-1). This leads to excess substrates, which are shunted toward synthesis of sex hormones. Decreased cortisol leads to loss of feedback inhibition, increased adrenocorticotropic hormone, and further stimulation of the conversion of cholesterol into sex hormone precursors.
What are the likely findings on laboratory testing in 21β-hydroxylase deficiency?
Hyponatremia and hyperkalemia are likely because mineralocorticoids (which are low in these patients) are responsible for the retention of sodium and the excretion of potassium. Salt wasting causes hypotension, which leads to activation of the renin-angiotensin system, resulting in elevated serum renin levels.
Is this an example of hermaphroditism or pseudohermaphroditism?
Pseudohermaphroditism is a condition in which an infant is born with the gonads of one sex and the external genitalia of the opposite sex (eg, normal female gonads but ambiguous, male-like external genitalia). True hermaphroditism (rare) occurs when the infant has both male and female gonadal tissue.
What is the appropriate treatment for this condition - 21β-hydroxylase deficiency?
Treatment consists of replacement of the deficient hormones.
What is the most likely diagnosis?
Addison disease, or primary adrenal insufficiency, is suggested by the clinical history of weakness and orthostatic hypotension and by the signs of hyperpigmentation, hyponatremia, hyperkalemia, and a low serum cortisol level.
What are 7 common etiologies of Addison’s disease?
Most cases of Addison disease are idiopathic or autoimmune related. Other causes include the following:
1. Disseminated intravascular coagulation.
2. Waterhouse-Friderichsen syndrome (hemorrhagic necrosis of the adrenal gland, classically due to meningococcemia).
3. Granulomatous diseases such as tuberculosis.
4. HIV infection.
5. Neoplasm.
6. Trauma.
7. Iatrogenic vascular disorders.
What is the cause of this patient’s metabolic abnormalities?
Adrenal insufficiency causes a deficiency of cortisol. Hyponatremia, hyperkalemia, and a low bicarbonate level can result from low aldosterone levels associated with primary adrenal insufficiency.
How would this patient, with Addisons disease, cortisol level change if she were administered adrenocorticotropic hormone (ACTH)?
The cortisol level should not change appreciably since it is low because of a primary adrenal insufficiency (ie, the problem is within the adrenal gland itself). This is suggested by the hyperpigmentation, which is due to the attempt of the pituitary gland to overcome the cortisol deficiency by increasing ACTH production. ACTH, in turn, stimulates the release of melanocyte-stimulating hormone, causing hyperpigmentation.
What are the secondary and tertiary forms of Addison’s disease?
Secondary adrenal insufficiency is caused by decreased ACTH secretion by the pituitary gland. Administration of ACTH results in a cortisol response. This syndrome does not cause hyperpigmentation. Tertiary adrenal insufficiency is caused by a decrease in corticotropin-releasing hormone production by the hypothalamus.
What is the most likely diagnosis?
Primary hyperaldosteronism, also known as Conn syndrome, is suggested by the patient’s history and her hypertension, hypernatremia, and hypokalemia. Approximately 30%–60% of cases are due to solitary adrenal adenomas in the zona glomerulosa, the aldosterone-secreting layer of the adrenal cortex. Bilateral hyperplasia of the zona glomerulosa can also cause Conn syndrome.
How is aldosterone regulated?
Renin, produced by the juxtaglomerular cells of the kidney, cleaves angiotensinogen (produced by the liver) to form angiotensin I. Angiotensin I, in turn, is cleaved by angiotensin-converting enzyme to form angiotensin II. In response to volume contraction, angiotensin II becomes a potent stimulator of aldosterone synthase, a key enzyme in aldosterone synthesis.
Other key stimuli of aldosterone secretion include decreased plasma sodium and increased plasma potassium.
Another patient presents with similar symptoms, but his laboratory tests show increased serum renin activity. What is his most likely diagnosis?
Another patient presents with similar symptoms, but his laboratory tests show increased serum renin activity. What is his most likely diagnosis?
Given the patient’s serum potassium level of 2.8mEq/L, what are the most likely findings on electrocardiogram (ECG)?
Typical ECG findings include prominent U waves, flattened T waves, and ST-segment depression (Figure 6-2).
What is the appropriate treatment for Primary hyperaldosteronism (Conn syndrome), and what are the adverse effects?
If a solitary, aldosterone-secreting adrenal adenoma is found, surgical resection (adrenalectomy) is indicated. Bilateral adrenal hyperplasia is treated medically with an aldosterone antagonist such as spironolactone. Major adverse effects of spironolactone are due to its antiandrogen effects, including gynecomastia, loss of libido, menstrual irregularities, and impotence.
What is the most likely diagnosis? 4 common causes?
Cushing syndrome results from excess glucocorticoids, either from increased cortisol production or exogenous glucocorticoid therapy. Common causes include the following:
1. Iatrogenic (eg, steroid ingestion, most common).
2. Pituitary adenoma (Cushing disease).
3. Adrenal tumor/hyperplasia.
4. Adrenocorticotropic hormone (ACTH)-producing tumor (most commonly secondary to small cell lung cancer).
What laboratory tests can help confirm the diagnosis of Cushing syndrome?
Screening tools for Cushing syndrome or glucocorticoid excess include the following:
1. 24-hour urine free cortisol test. Elevated cortisol level indicates hypercortisolism.
2. Dexamethasone suppression test. A normal result is a decrease in cortisol after administration of low- dose dexamethasone. In glucocorticoid excess due to Cushing disease, low-dose dexamethasone will
not suppress cortisol levels.
After identifying elevated cortisol levels, what diagnostic tests help define the source of the hormonal abnormality?
What are the appropriate treatments for Cushing syndrome?
The most appropriate treatment for adrenal tumors is surgery. Treatments for nonresectable tumors or hyperplasia are as follows:
1. Ketoconazole: Inhibits glucocorticoid production.
2. Metyrapone: Inhibits cortisol formation in adrenal pathway.
3. Aminoglutethimide: Inhibits the synthesis of steroids.
What is the regular cycle of cortisol levels in the body?
Cortisol levels peak in the early morning (approximately 8 AM) and reach their lowest levels at midnight. Basal body temperature fluctuates with the cortisol cycle (Figure 6-3).
What is the most likely diagnosis?
Autoimmune destruction of pancreatic islet cells results in insulin deficiency (Figure 6-4), leading to type 1 diabetes mellitus (DM). Common presenting symptoms include polydipsia, polyphagia, weight loss, and polyuria (osmotic diuresis secondary to glycosuria).
What are the two types of Diabetes Mellitus?
Type 1 DM is characterized by absolute insulin deficiency; type 2 DM is characterized by insulin resistance and increased insulin levels. Type 1 DM typically presents in thin individuals younger than 30 years of age. Type 2 DM typically affects obese individuals older than 30 years of age (although it is increasingly seen among younger obese individuals). Both types of diabetes can result in retinopathy, nephropathy, and neuropathy.
What is diabetic ketoacidosis (DKA)?
DKA is a life-threatening complication of uncontrolled type 1 DM. In the absence of insulin, increased levels of fatty acids are delivered to the liver, where ketogenesis occurs. This lowers the pH of the blood. Presenting symptoms include Kussmaul hyperpnea (deep respirations), abdominal pain, dehydration, and nausea/vomiting. Patients may have a sweet/fruity/alcoholic odor to their breath.
What is the appropriate treatment for DKA?
Acute DKA requires rapid fluid resuscitation with normal saline, followed by the administration of intravenous insulin and repletion of depleted electrolytes, especially potassium. Administration of bicarbonate to correct the acidic blood pH is usually not recommended unless the acidosis is severe.
Following an episode of DKA, lifelong insulin replacement is required for patients diagnosed with type 1 DM. Oral hypoglycemic agents are effective in type 2 DM but not in type 1.
What electrolyte abnormalities are frequently associated with DKA?
DKA is associated with depletion of total body potassium stores through osmotic diuresis. Serum potassium levels may appear normal or elevated even though total body potassium stores are low; this is because intracellular potassium is shifted into the extracellular space in exchange for hydrogen ions to buffer the effects of metabolic acidosis. Treatment of DKA with insulin drives potassium back into cells, and patients undergoing treatment for DKA can thus become profoundly hypokalemic.
What is the most likely diagnosis?
Gigantism, which is caused by excess growth hormone (GH). In patients with fused epiphyses (ie, growth plates), the disease is called acromegaly. In older patients, physical changes may go unnoticed until hats, gloves, and shoes no longer fit.
What is the pathophysiology of growth hormone excess (gigantism/acromegaly)?
Excess GH can arise from pituitary excess, hypothalamic GH-releasing hormone (GHRH) excess, or an ectopic source. A genetic component of the disease is suggested by the high levels of GH seen in McCune- Albright syndrome and multiple endocrine neoplasia type I.
How is Growth Hormone produced?
GH is produced and stored in the acidophilic cells of the anterior pituitary. Basophilic cells in the anterior pituitary can be recalled with the mnemonic B-FLAT. Basophils: Follicle-stimulating hormone, Luteinizing hormone, Adrenocorticotropic hormone, and Thyroid-stimulating hormone. Acidophils: GH and prolactin.
How is secretion of Growth Hormone controlled?
GH is released in a pulsatile fashion. Secretion is controlled by the hypothalamus (Figure 6-5). GHRH stimulates GH production. Somatostatin interferes with its effect on the pituitary. Insulin-like growth factor-1 (IGF-1) exerts negative feedback to inhibit GH secretion. At puberty, the frequency and amplitude of GH secretory pulses increase because of gonadal hormones. The combination drives the “growth spurt.”
How is Growth Hormone excess (gigantism/acromegaly) diagnosed?
What is the most likely diagnosis?
Graves disease.
What demographic group does Graves typically affect?
Graves disease occurs eight times more frequently in women than men. The prevalence is higher in populations with a high iodine intake. The disease rarely occurs before adolescence and typically affects individuals in the fourth to sixth decades of life.
What is the pathophysiology of Graves?
It is caused by autoimmune-induced hyperthyroidism. Immunoglobulins mimic thyroid-stimulating hormone (TSH) and activate the TSH receptor.
What are other common causes of hyperthyroidism other than Graves? (5)
What are the appropriate treatments for Graves?
Graves disease can remit and recur. Effective treatment includes thyroidectomy, thyroid-inhibiting medications, or radioactive iodine ablation (radioactive iodine is taken up by, and then destroys, hyperfunctioning thyroid tissue).
Medications such as propylthiouracil (PTU) and methimazole inhibit iodine organification and coupling in the thyroid. PTU and steroids also inhibit the peripheral conversion of thyroxine to triiodothyronine.
What is thyroid storm?
Thyroid storm is an acute, life-threatening surge of thyroid hormone in the blood, usually precipitated by surgery, trauma, infection, acute iodine load, or long-standing hyperthyroidism. Manifestations include tachycardia (> 140/min), heart failure, fever, agitation, delirium, psychosis, stupor, and/or coma. Gastrointestinal symptoms can also be present. This condition is treated with methimazole and agents that reduce peripheral conversion of T4 to triiodothyronine.
What is the most striking laboratory finding?
Hypercalcemia. Common causes of hypercalcemia are: Malignancy, Intoxication with vitamin D, Sarcoidosis, Hyperparathyroidism, Alkali syndrome, and Paget disease of bone (mnemonic: MISHAP). In outpatients, hyperparathyroidism is the most common cause of hypercalcemia; in inpatients, malignancy is the most common cause.
The patient is found to have elevated PTH and normal creatine. How does this help explain her clinical presentation?
The patient has primary hyperparathyroidism (Table 6-2), as evidenced by high PTH, high calcium, and normal renal function. To recall the symptoms of hyperparathyroidism (and hypercalcemia in general) use the following mnemonic: “Painful bones, renal stones (nephrolithiasis), abdominal groans (abdominal pain, nausea, vomiting, and anorexia), psychic moans (changes in mental status, concentration, and mood), and fatigue overtones.”
What is the most likely diagnosis?
The patient’s cold intolerance, weight gain, myxedema, fatigue, prolonged relaxation phase of deep tendon reflexes, and low free T4 with high TSH suggest primary hypothyroidism.
What is the most likely diagnosis?
Metabolic syndrome, also known as dysmetabolic syndrome, syndrome X, and insulin resistance syndrome.
What are the diagnostic criteria for Metabolic syndrome?
What do the skin findings seen in Metabolic syndrome represent?
Acanthosis nigricans is a common physical sign of insulin resistance, particularly in Hispanics and African Americans. It may be due to high levels of circulating insulin or insulin-like growth factor receptors in the skin. Other conditions with acanthosis nigricans include polycystic ovarian syndrome and some visceral malignancies.
What is the most likely diagnosis?
Multiple endocrine neoplasia (MEN) type IIA, or Sipple syndrome, is characterized by medullary carcinoma of the thyroid, pheochromocytoma, and hyperparathyroidism (due to either hyperplasia or tumor). Medullary carcinoma of the thyroid is characterized by nests of cells in amyloid stroma. Figure 6-7 shows the lobular pattern of growth of this tumor. Table 6-3 presents MEN types.
What is the most likely diagnosis?
Pheochromocytoma is a catecholamine-secreting tumor of chromaffin cells of the adrenal medulla.
What are the key steps in epinephrine catabolism?
Catecholamines are substrates for monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) (Figure 6-8). Epinephrine can undergo two paths of catabolism. In the first, COMT converts epinephrine into metanephrine, which MAO then converts into 3-methoxy-4- hydroxymandelic acid. In the second, MAO converts epinephrine into dihydroxymandelic acid, which COMT then converts into 3-methoxy-4- hydroxymandelic acid (the same product as the first pathway).
What is the most likely diagnosis?
Pseudohypoparathyroidism (type 1a) is characterized by renal unresponsiveness to PTH. A genetic cause of this disorder results from a mutation in the Gs-a1 protein of adenylyl cyclase. McCune-Albright hereditary osteodystrophy is also present in type 1a pseudohypoparathyroidism, and some patients have growth hormone–releasing hormone resistance.
What is the most likely diagnosis?
Non-insulin-dependent (type 2) diabetes mellitus (NIDDM).
What are the diagnostic criteria for TIIDM?
What is the production and structure of insulin?
Insulin is originally produced as pre-proinsulin in the pancreas. During posttranslational processing, a signal peptide is removed, producing proinsulin. Proinsulin contains two polypeptide chains connected by two sulfhydryl bonds (cysteine to cysteine) and a C-peptide. In the conversion from proinsulin (the zymogen) to active insulin, the C-peptide is cleaved off (Figure 6-9). Synthetic insulin lacks the C-peptide. Therefore, measuring C-peptide is useful in patients in whom surreptitious insulin injection is suspected (factitious hypoglycemia).
How does insulin exert its effects on organs?
The insulin receptor is a heterodimer of α and β subunits. The β subunit is a tyrosine kinase. When insulin binds, this subunit autophosphorylates itself, leading to activation of downstream signaling cascades. Insulin stimulates glucose storage as glycogen in the liver, triglyceride storage in adipose tissue, and amino acid storage as protein in muscle. It also promotes utilization of glucose in muscle for energy (Figure 6-10).
What is the most likely diagnosis?
What is the likely cause?
Sheehan syndrome - This patient’s massive hemorrhage during pregnancy likely led to ischemia and necrosis of the pituitary gland.
What is the significance of the patient’s vital signs?
The patient displays orthostatic hypotension, defined as a systolic blood pressure decrease of at least 20 mm Hg systolic (or a diastolic blood pressure decrease of 10 mm Hg) within 3 minutes of standing. There is a compensatory increase in heart rate to maintain peripheral perfusion. The cause of hypotension in this patient is loss of cortisol, which is required for maintenance of peripheral vascular tone. This is a medical emergency, as the patient is at risk for vascular collapse.
What is the most likely diagnosis?
What is the differential diagnosis?
Thyroglossal duct cyst.
The differential for benign midline neck masses is vast, including thyroglossal duct cysts, dermoid cysts, sebaceous cysts, ectopic thyroid tissue, midline branchial cleft cysts (usually are lateral), lipomas, and lymphadenopathy.
Hint: If the question describes a lateral neck mass in a patient with a webbed neck, shield chest, short stature, and coarctation of the aorta, think Turner syndrome. The neck mass is likely to be a cystic hygroma.
How does the thyroid gland form during development?
The thyroid is derived from endoderm at the foramen cecum,
the junction between the developing anterior and posterior
tongue. The thyroid descends to its final position over the trachea by the seventh week of gestation, and its pharyngeal connection forms a stalk called the thyroglossal duct (Figure
6-11).
What is the most likely diagnosis?
Papillary thyroid cancer.
Care must be taken during thyroidectomy not to remove all functioning parathyroid gland tissue. How many parathyroid glands are there?
Most people (85%) have four parathyroid glands. However, 13%–15% of people have more than four glands, and less than 2% of people have fewer than four glands.
What nerves in this region are particularly at risk during thyroidectomy?
Damage to the recurrent laryngeal nerve in the tracheoesophageal groove results in a hoarse voice. The external laryngeal branch of the superior laryngeal nerve accompanies the superior thyroid artery and therefore can be ligated with the artery in thyroid surgery (Figure 6-12). It is spared by ligating the artery close to the gland. Damage results in changes in pitch and reduction in voice volume.
What is the most likely diagnosis?
Plummer disease (also known as toxic multinodular goiter) is the second most common cause of hyperthyroidism in the Western world after Graves disease and the number one cause among the elderly and in endemic areas of iodine deficiency. This is not to be confused with the uncommon Plummer-Vinson syndrome (esophageal web plus iron deficiency anemia).
How does the physical examination help establish a differential diagnosis?
Patients with Graves disease typically have a diffusely enlarged painless goiter rather than a multinodular goiter. Exophthalmos, pretibial myxedema, and acropachy (thickening of peripheral tissues), characteristic of Graves disease, are absent in Plummer disease. Subacute thyroiditis (also known as de Quervain thyroiditis) presents with an enlarged painful goiter (Figure 6-13), neck pain, and fever, frequently after a viral illness such as mumps or coxsackievirus. The erythrocyte sedimentation rate is typically elevated, and the condition resolves with time and use of nonsteroidal anti-inflammatory drugs.
