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USMLE First Aid
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- Hypopituitarism Undersecretion of pituitary hormones due to:- Nonsecreting pituitary adenoma, craniopharyngioma- Sheehan syndrome – ischemic infarct of pituitary following postpartum bleeding; pregnancy-induced pituitary ...
- Thyroid development Thyroid diverticulum arises from floor of primitive pharynx and descends into neck. - Connected to tongue by thyroglossal duct, which normally disappears but may persist as cysts or the pyramidal lobe ...
- Anterior pituitary (adenohypophysis) Secretes FSH, LH, ACTH, TSH, PRL, GH, and β-endorphin. - Melanotropin (MSH) secreted from intermediate lobe of pituitary. - Basophils: FSH, LH, ACTH, TSH- Acidophils: GH, PRL - Derived from oral ectoderm ...
- Posterior pituitary (neurohypophysis) Stores and releases vasopressin (antidiuretic hormone, or ADH) and oxytocin, both made in the hypothalamus.- ADH is made in the supraoptic nuclei.- Oxytocin is made in the paraventricular nuclei. - Transported ...
- Endocrine pancreas cell types Islets of Langerhans are collections of α, β, and δ endocrine cells. Islets arise from pancreatic buds. α = glucagon (peripheral)β = insulin (central)δ = somatostatin (interspersed)
- Insulin Synthesis: Preproinsulin (synthesized in RER) → cleavage of "presignal" → proinsulin (stored in secretory granules) → cleavage of proinsulin → exocytosis of insulin and C-peptide equally. ...
- Hypothalamic-pituitary hormones CRH: ↑ ACTH, MSH, β-endorphin- ↓ in chronic exogenous steroid use Dopamine: ↓ prolactin, TSH- Dopamine antagonists (eg, antipsychotics) can cause galactorrhea due to hyperprolactinemia GHRH: ↑ ...
- Growth hormone (somatotropin) Secreted by anterior pituitary. Function: Stimulates linear growth and muscle mass through IGF-1 (somatomedin C) secretion by liver. ↑ insulin resistance (diabetogenic).- IGF-1 (somatomedin) increases ...
- Ghrelin Stimulates hunger (orexigenic effect) and GH release (via GH secretagogue receptor). - Activated neuropeptide Y (orexigenic) Produced by stomach. Sleep deprivation or Prader-Willi syndrome → ↑ ...
- Leptin Satiety hormone. Produced by adipose tissue.- Decreases hypothalamic neuropeptide Y, which is a potent activator of feeding (orexigenic). Mutation of leptin gene → congenital obesity. Sleep deprivation ...
- Endocannabinoids Act at cannabinoid receptors in hypothalamus and nucleus accumbens, two key brain areas for the homeostatic and hedonic control of food intake. ↑ appetite
- 17α-hydroxylase deficiency ↑ Mineralocorticoids↓ Cortisol↓ Sex hormones↑ BP↓ K+Labs: ↓ androstenedione Presentation: - XY: ambiguous genitalia, undescended testes- XX: lacks 2° sexual development All congenital adrenal ...
- 21-hydroxylase deficiency ↓ Mineralcorticoids↓ Cortisol↑ Sex hormones↓ BP↑ K+ Labs: ↑ renin activity, ↑ 17-hydroxyprogesterone Presentation: - Most common- Presents in infancy (salt wasting) or in childhood (precocious ...
- 11β-hydroxylase deficiency ↓ Aldosterone↑ 11-deoxycorticosterone (results in ↑ BP)↓ Cortisol↑ Sex hormones↑ BP↓ K+ Labs: ↓ renin activity Presentation: - XX: virilization All congenital adrenal enzyme deficiencies ...
- Cortisol Source: Adrenal zona fasciculata. Bound to corticosteroid-binding globulin. Function: ↑ Appetite↑ Blood pressure- Upregulates α1 receptors on arterioles → ↑ sensitivity to norepinephrine and ...
- Calcium homeostasis Plasma Ca2+ consists in three forms:- Ionized/free (~45%, active form)- Bound to albumin (~40%)- Bound to anions (~15%) ↑ in pH → ↑ affinity of albumin (↑ negative charge) to bind Ca2+ → ...
- Parathyroid hormone Source: Chief cells of parathyroid. Function: ↑ bone resorption of Ca2+ and PO43-.↑ kidney reabsorption of Ca2+ in distal convoluted tubule.↓ reabsorption of PO43- in proximal convoluted tubule.↑ ...
- Calcitonin Source: Parafollicular cells (C cells) of thyroid. Function: ↓ bone resorption of Ca2+.Calcitonin opposes actions of PTH. Not important in normal Ca2+ homeostasis. Regulation: ↑ serum Ca2+ → ...
- Thyroid hormones (T3/T4) Iodine-containing hormones that control the body's metabolic rate.T4 major form in blood (longer half-life), conversion to T3 (more potent) Source: Follicles of thyroid. 5'-deiodinase converts T4 (the ...
- Signaling pathways - cAMP FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2-receptor), MSH, PTH, calcitonin, GHRH, glucagon
- Signaling pathways - cGMP BNP, ANP, EDRF (NO)
- Signaling pathways - IP3 GnRH, oxytocin, ADH (V1-receptor), TRH, histamine (H1-receptor), angiotensin II, gastrin
- Signaling pathways - Intracellular receptor Progesterone, estrogen, testosterone, cortisol, aldosterone, T3/T4, vitamin D
- Signaling pathways - Receptor tyrosine kinase Insulin, IGF-1, FGF, PDGF, EGF - MAP kinase pathway - Think growth factors
- Signaling pathways - Nonreceptor tyrosine kinase Prolactin, immunomodulators (eg, cytokines IL-2, IL-5, IFN), GH, G-CSF, erythropoietin, thrombopoietin - JAK/STAT pathway - Think acidophils (prolactin, GH) and cytokines
- Signaling pathway - Steroid hormones Steroid hormones are lipophilic and therefore must circulate bound to specific binding globulins, which ↑ their solubility. In men, ↑ sex hormone-binding globulin (SHBG) lowers free testosterone → ...
- Cushing syndrome Etiology: ↑ cortisol due to:- Exogenous corticosteroids: result in ↓ ACTH, bilateral adrenal atrophy. Most common cause.- Primary adrenal adenoma, hyperplasia, or carcinoma – result in ↓ ACTH, ...
- Adrenal insufficiency Inability of adrenal glands to generate enough glucocorticoids +/- mineralocorticoids for the body's needs. Symptoms include weakness, fatigue, orthostatic hypotension, muscle aches, weight loss, GI ...
- Primary adrenal insufficiency Deficiency of aldosterone and cortisol production due to loss of gland function → hypotension (hyponatremic volume contraction), hyperkalemia, metabolic acidosis, skin and mucosal hyperpigmentation ...
- Secondary adrenal insufficiency Seen with ↓ pituitary ACTH production. No skin/mucosal hyperpigmentation, no hyperkalemia (aldosterone synthesis preserved due to intact renin-angiotensin-aldosterone axis).
- Tertiary adrenal insufficiency Seen in patients with chronic exogenous steroid use, precipitated by abrupt withdrawal. Aldosterone synthesis unaffected.
- Hyperaldosteronism Increased secretion of aldosterone from adrenal gland. Clinical features: hypertension, fatigue, muscle weakness, paresthesias, headaches, ↓ or normal K+, metabolic alkalosis. 1° hyperaldosteronism ...
- Neuroendocrine tumors Heterogeneous group of neoplams originating from Kulchitsky and enterochromaffin-like cells. Most tumors arise in the GI system (eg, carcinoid, gastrinoma), pancreas (eg, insulinoma, glucagonoma), ...
- Neuroblastoma Most common tumor of the adrenal medulla in children, usually <4 years old. Originates from neural crest cells. Occurs anywhere along the sympathetic chain. Most common presentation:- Abdominal distension ...
- Pheochromocytoma Most comon tumor of the adrenal medulla in adults. Derived from chromaffin cells (arise from neural crest).Up to 25% of cases associated with germline mutations (eg, NF-1, VHL, RET [MEN 2A, 2B]). Symptoms: - ...
- Causes of goiter Smooth/diffuse:- Graves disease- Hashimoto thyroiditis- Iodine deficiency- TSH-secreting pituitary adenoma Nodular:- Toxic multinodular goiter- Thyroid adenoma- Thyroid cancer- Thyroid cyst
- Hashimoto thyroiditis Most common cause of hypothyroidism in iodine-sufficienct regions.An autoimmune disorder with antithyroid peroxidase (antimicrosomal) and antithyroglobulin antibodies.- Associated with HLA-DR3, DR5.- ...
- Congenital hypothyroidism (cretinism) Severe fatal hypothyroidism due to antibody-mediated maternal hypothyroidism, thyroid agenesis, thyroid dysgenesis (most common cause in US), iodine deficiency, dyshormonogenetic goiter. Findings: the ...
- Subacute granulomatous thyroiditis (de Quervain) Self-limited disease often following a flu-like illness (eg, viral infection). May be hyperthyroid early in course, followed by hypothyroidism (permanent in ~15% of cases).- Do not have increased radioactive ...
- Riedel thyroiditis Thyroid replaced by fibrous tissue with inflammatory infiltrate.Fibrosis may extend to local structures (eg, trachea, esophagus), mimicking anaplastic carcinoma. 1/3 are hypothyroid. Considered a manifestation ...
- Wolff-Chaikoff effect Thyroid gland downregulation in response to ↑ iodide. Excess iodine temporarily inhibits thyroid peroxidase → ↓ iodine organification → T3/T4 production. Opposite of Jod-Basedow phenomenon. ...
- Graves disease Most common cause of hyperthyroidism.Thyroid-stimulating immunoglobulin (IgG; type II hypersensitivity) stimulates TSH receptors on thyroid (hyperthyroidism, diffuse goiter) and dermal fibroblasts (pretibial ...
- Toxic multinodular goiter Focal patches of hyperfunctioning follicular cells distended with colloid working independently of TSH (due to TSH receptor mutations in 60% of cases). ↑ release of T3 and T4. Hot nodules are rarely ...
- Thyroid storm Uncommon but serious complication that occurs when hyperthyroidism is incompletely treated/untreated and then significantly worsens in the setting of acute stress such as infection, trauma, surgery. Presents ...
- Jod-Basedow phenomenon Thyrotoxicosis if a patient with iodine deficiency and partially autonomous thyroid tissue (eg, autonomous nodule) is made iodine replete. Can happen after iodine IV contrast. Opposite to Wolff-Chaikoff ...
- Thyroid cancer Papillary, follicular, medullary, undifferentiated/anaplastic Typically diagnosed with fine needle aspiration; treated with thyroidectomy. Complications of sugery:- Hoarseness (due to recurrent laryngeal ...
- Thyroid adenoma Benign solitary growth of the thyroid. Most are nonfunctional ("cold"), can rarely cause hyperthyroidism via autonomous thyroid hormone production ("hot" or "toxic"). Most common histology is follicular; ...
- Hypoparathyroidism Due to acciental surgical excision of parathyroid glands, autoimmune destruction, or DiGeorge syndrome. Findings: tetany, hypocalcemia, hyperphosphatemia.- Chvostek sign – tapping of facial nerve → ...
- Pseudohypoparathyroidism type 1A Also known as Albright hereditary osteodystrophy. Unresponsiveness of kidney to PTH → hypocalcemia despite ↑ PTH levels- Due to defective GS protein α-subunit causing end-organ resistance to PTH- ...
- Pseudopseudohypoparathyroidism Physical exam features of Albright hereditay osteodystrophy (shortened 4th/5th digits, short stature) but without end-organ PTH resistance (PTH levels normal). - Occurs when defective Gs protein α-subunit ...